Page last updated: 2024-10-30

metformin and Body Weight

metformin has been researched along with Body Weight in 680 studies

Metformin: A biguanide hypoglycemic agent used in the treatment of non-insulin-dependent diabetes mellitus not responding to dietary modification. Metformin improves glycemic control by improving insulin sensitivity and decreasing intestinal absorption of glucose. (From Martindale, The Extra Pharmacopoeia, 30th ed, p289)
metformin : A member of the class of guanidines that is biguanide the carrying two methyl substituents at position 1.

Body Weight: The mass or quantity of heaviness of an individual. It is expressed by units of pounds or kilograms.

Research Excerpts

ExcerptRelevanceReference
"In overweight or obese patients with T2DM, a once-weekly subcutaneous administration of PEG-Loxe for 16 weeks, in addition to lifestyle interventions or oral antidiabetic drug therapy, resulted in significantly greater weight loss compared to metformin."9.69Short-term effect of polyethylene glycol loxenatide on weight loss in overweight or obese patients with type 2 diabetes: An open-label, parallel-arm, randomized, metformin-controlled trial. ( Cai, H; Chen, Q; Duan, Y; Zhang, X; Zhao, Y, 2023)
"We aimed to determine the efficacy and safety of DDG combined with metformin for the treatment of T2DM patients with obesity."9.69Effectiveness and safety of Daixie Decoction granules combined with metformin for the treatment of T2DM patients with obesity: study protocol for a randomized, double-blinded, placebo-controlled, multicentre clinical trial. ( Liu, Z; Wang, F; Wang, L; Wang, M; Zhang, J; Zhang, K; Zhang, Y; Zhou, S; Zhou, Y, 2023)
"Here we study whether circulating GDF-15 levels were raised by such metformin treatment and whether they related to changes in body weight and visceral fat in children with obesity."9.51A 24-month metformin treatment study of children with obesity: Changes in circulating GDF-15 and associations with changes in body weight and visceral fat. ( Bassols, J; Carreras-Badosa, G; de Zegher, F; Díaz-Roldán, F; Gómez-Vilarrubla, A; Ibañez, L; López-Bermejo, A; Martínez-Calcerrada, JM; Mas-Parés, B; Prats-Puig, A; Puerto-Carranza, E; Xargay-Torrent, S, 2022)
"The glucose-lowering drug metformin has recently been shown to reduce myocardial oxygen consumption and increase myocardial efficiency in chronic heart failure (HF) patients without diabetes."9.41Metformin Lowers Body Weight But Fails to Increase Insulin Sensitivity in Chronic Heart Failure Patients without Diabetes: a Randomized, Double-Blind, Placebo-Controlled Study. ( Brøsen, K; Bøtker, HE; Dollerup, OL; Frøkiær, J; Hansson, NH; Jespersen, NR; Jessen, N; Larsen, AH; Møller, N; Nørrelund, H; Wiggers, H, 2021)
"Metformin treatment (1000-2000 mg/day) over 6 months in pubertal children and/or adolescents with obesity and hyperinsulinism is associated with a reduction in body mass index (BMI) and the insulin resistance index (HOMA-IR)."9.30Effects of metformin administration on endocrine-metabolic parameters, visceral adiposity and cardiovascular risk factors in children with obesity and risk markers for metabolic syndrome: A pilot study. ( Bassols, J; Carreras-Badosa, G; de Zegher, F; Díaz-Roldán, F; Dorado-Ceballos, E; Ibáñez, L; López-Bermejo, A; Martínez-Calcerrada, JM; Mas-Parés, B; Osiniri, I; Prats-Puig, A; Xargay-Torrent, S, 2019)
"This study provides evidence that, compared to glimepiride, saxagliptin more effectively achieves a composite endpoint of adequate glycaemic control without hypoglycaemia and without weight gain in T2D patients who are inadequately controlled with metformin monotherapy, especially in overweight patients with moderate hyperglycaemia and a relatively short duration of diabetes."9.30Comparative effect of saxagliptin and glimepiride with a composite endpoint of adequate glycaemic control without hypoglycaemia and without weight gain in patients uncontrolled with metformin therapy: Results from the SPECIFY study, a 48-week, multi-centr ( Bi, Y; Cheng, J; Gu, T; Li, D; Ma, J; Shao, J; Shi, B; Sun, Z; Xu, L; Zhang, H; Zhang, Q; Zhong, S; Zhu, D; Zhu, L, 2019)
"Metformin treatment significantly reduced LVMI, LVM, office systolic BP, body weight, and oxidative stress."9.30A randomized controlled trial of metformin on left ventricular hypertrophy in patients with coronary artery disease without diabetes: the MET-REMODEL trial. ( Al-Talabany, S; Baig, F; Bhalraam, U; Choy, AM; Gandy, SJ; George, J; Houston, JG; Hussain, MS; Khan, F; Lang, CC; Matthew, S; McKinnie, A; Mohan, M; Mordi, IR; Singh, JSS; Struthers, AD, 2019)
"This post hoc analysis assessed the effects on cardiovascular risk factors of body weight, systolic blood pressure (SBP) and triglycerides after 28 weeks' treatment with exenatide once weekly plus dapagliflozin, as compared with exenatide once weekly or dapagliflozin, in patient subpopulations from the DURATION-8 trial of patients with type 2 diabetes mellitus (T2DM) inadequately controlled with metformin alone."9.27Effects of exenatide once weekly plus dapagliflozin, exenatide once weekly, or dapagliflozin, added to metformin monotherapy, on body weight, systolic blood pressure, and triglycerides in patients with type 2 diabetes in the DURATION-8 study. ( Ahmed, A; Frías, JP; Guja, C; Hardy, E; Jabbour, SA; Öhman, P, 2018)
" Although there is evidence for weight loss with metformin for people with obesity who are already taking clozapine, there have been no published trials that have investigated the effect of metformin in attenuating weight gain at the time of clozapine initiation."9.27CoMET: a protocol for a randomised controlled trial of co-commencement of METformin as an adjunctive treatment to attenuate weight gain and metabolic syndrome in patients with schizophrenia newly commenced on clozapine. ( Baker, A; Flaws, D; Friend, N; Kisely, S; Lim, C; McGrath, JJ; Moudgil, V; Patterson, S; Russell, A; Sardinha, S; Siskind, D; Stedman, T; Suetani, S; Winckel, K, 2018)
"Proof-of-concept study to investigate the amplifying effects of diazoxide (DZX)-mediated insulin suppression on lifestyle-induced weight loss in nondiabetic, hyperinsulinemic, obese men."9.27High-Dose, Diazoxide-Mediated Insulin Suppression Boosts Weight Loss Induced by Lifestyle Intervention. ( Brandon, T; de Boer, H; Filius, M; Hermus, A; Loves, S; Mekking, M; Tack, CJ; van Groningen, L, 2018)
"Steady-state population pharmacokinetics of a noncommercial immediate-release metformin (hydrochloride) drug product were characterized in 28 severely obese children with insulin resistance."9.24Effects of SLC22A1 Polymorphisms on Metformin-Induced Reductions in Adiposity and Metformin Pharmacokinetics in Obese Children With Insulin Resistance. ( Alfaro, RM; Calis, KA; Hon, YY; Reynolds, JC; Roza, O; Sam, WJ; Yanovski, JA, 2017)
" In this study, data were pooled from two randomized, placebo-controlled trials, which were originally designed to examine the efficacy of metformin in treating antipsychotic-induced weight gain and other metabolic abnormalities."9.22Metformin treatment of antipsychotic-induced dyslipidemia: an analysis of two randomized, placebo-controlled trials. ( Chan, PK; Gao, KM; Guo, WB; Jin, H; Ou, JJ; Shao, P; Wu, RR; Zhang, FY; Zhao, JP, 2016)
"Our results show that Metformin and acupuncture combined therapy significantly improves body weight, body mass index (BMI), fasting blood sugar (FBS), fasting insulin (FINS), homeostasis model assessment (HOMA) index, interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), leptin, adiponectin, glucagon-like peptide-1 (GLP-1), resistin, serotonin, free fatty acids (FFAs), triglyceride (TG), low-density lipoprotein cholesterol (LDLc), high-density lipoprotein cholesterol (HDLc) and ceramides."9.22Comparative evaluation of the therapeutic effect of metformin monotherapy with metformin and acupuncture combined therapy on weight loss and insulin sensitivity in diabetic patients. ( Firouzjaei, A; Li, GC; Liu, WX; Wang, N; Zhu, BM, 2016)
"To evaluate the proportion of patients with type 2 diabetes mellitus (T2DM) achieving reductions in both glycated hemoglobin (HbA1c) and body weight with canagliflozin, a sodium glucose co-transporter 2 inhibitor, versus sitagliptin over 52 weeks."9.22Canagliflozin provides greater attainment of both HbA1c and body weight reduction versus sitagliptin in patients with type 2 diabetes. ( Canovatchel, W; Davidson, JA; Jodon, H; Lavalle-González, FJ; Qiu, R; Schernthaner, G; Vijapurkar, U, 2016)
"The study will evaluate whether metformin can result in favorable changes in breast density, select proteins and hormones, products of body metabolism, and body weight and composition."9.22Phase II study of metformin for reduction of obesity-associated breast cancer risk: a randomized controlled trial protocol. ( Altbach, M; Chalasani, P; Chow, HH; Galons, JP; Martinez, JA; Roe, D; Stopeck, A; Thompson, PA; Thomson, CA; Villa-Guillen, DE, 2016)
"Metformin has been used for alleviating metabolic abnormalities in patients with schizophrenia."9.22Effects of Low Dose Metformin on Metabolic Traits in Clozapine-Treated Schizophrenia Patients: An Exploratory Twelve-Week Randomized, Double-Blind, Placebo-Controlled Study. ( Chen, CH; Chen, PY; Chiu, CC; Huang, MC; Lin, SK; Lin, YK; Lu, ML, 2016)
" This study was conducted as an exploratory analysis to clarify the effects of liraglutide, a GLP-1RA, on beta cell function, fat distribution and pancreas volume compared with metformin in Japanese overweight/obese patients with T2DM."9.20Effects of Liraglutide Monotherapy on Beta Cell Function and Pancreatic Enzymes Compared with Metformin in Japanese Overweight/Obese Patients with Type 2 Diabetes Mellitus: A Subpopulation Analysis of the KIND-LM Randomized Trial. ( Cobelli, C; Irie, J; Itoh, H; Jinzaki, M; Kawai, T; Manesso, E; Meguro, S; Saisho, Y; Sugiura, H; Tanaka, K; Tanaka, M, 2015)
"The effect of metformin on weight reduction in polycystic ovary syndrome (PCOS) is often unsatisfactory."9.19Short-term combined treatment with liraglutide and metformin leads to significant weight loss in obese women with polycystic ovary syndrome and previous poor response to metformin. ( Janez, A; Jensterle Sever, M; Kocjan, T; Kravos, NA; Pfeifer, M, 2014)
"To study the effect of metformin on metabolic parameters, body weight (BW), and waist circumference (WC) in patients with abdominal obesity (AO)."9.19[Efficacy of metformin in abdominal obesity]. ( Kichigin, VA; Markova, TN; Mkrtumian, AM; Podachina, SV; Zhuchkova, SM, 2014)
"Many studies have shown that metformin can decrease body weight and improve metabolic abnormalities in patients with schizophrenia."9.17Effects of adjunctive metformin on metabolic traits in nondiabetic clozapine-treated patients with schizophrenia and the effect of metformin discontinuation on body weight: a 24-week, randomized, double-blind, placebo-controlled study. ( Chen, CH; Chiu, CC; Huang, MC; Kao, CF; Kuo, PH; Lin, SK; Lu, ML, 2013)
"Compared with metformin, exenatide is better to control blood glucose, reduces body weight and improves hepatic enzymes, attenuating NAFLD in patients with T2DM concomitant with NAFLD."9.17Exenatide improves type 2 diabetes concomitant with non-alcoholic fatty liver disease. ( Fan, H; Pan, Q; Xu, Y; Yang, X, 2013)
"We tested genetic associations with weight loss and weight regain in the Diabetes Prevention Program, a randomized controlled trial of weight loss-inducing interventions (lifestyle and metformin) versus placebo."9.16Genetic predictors of weight loss and weight regain after intensive lifestyle modification, metformin treatment, or standard care in the Diabetes Prevention Program. ( Delahanty, LM; Florez, JC; Franks, PW; Jablonski, KA; Kahn, SE; Knowler, WC; McCaffery, JM; Pan, Q; Shuldiner, A; Watson, KE, 2012)
" The body weight, body mass index, fasting insulin and insulin resistance index decreased significantly in the metformin group, but increased in the placebo group during the 12-week follow-up period."9.16Metformin for treatment of antipsychotic-induced weight gain: a randomized, placebo-controlled study. ( Liang, GM; Tong, JH; Wang, M; Wang, XZ; Yan, HF; Zhu, G, 2012)
"Eighty-four women (ages 18-40 years) with first-episode schizophrenia who suffered from amenorrhea during antipsychotic treatment were randomly assigned, in a double-blind study design, to receive 1000 mg/day of metformin or placebo in addition to their antipsychotic treatment for 6 months."9.16Metformin for treatment of antipsychotic-induced amenorrhea and weight gain in women with first-episode schizophrenia: a double-blind, randomized, placebo-controlled study. ( Chan, PK; Davis, JM; Gao, K; Guo, XF; Jin, H; Ou, JJ; Shao, P; Twamley, EW; Wang, J; Wu, RR; Zhao, JP, 2012)
" This study aimed to determine the effect of metformin on body weight, body composition, metabolic risk factors and reproductive hormone levels in overweight or obese young women compared to placebo and comprehensive lifestyle intervention."9.15The effect of comprehensive lifestyle intervention or metformin on obesity in young women. ( Clifton, PM; Lim, SS; Noakes, M; Norman, RJ, 2011)
"Metformin had modest but favorable effects on body weight, body composition, and glucose homeostasis in obese insulin-resistant children participating in a low-intensity weight-reduction program."9.15Effects of metformin on body weight and body composition in obese insulin-resistant children: a randomized clinical trial. ( Brady, SM; Calis, KA; Kozlosky, M; Krakoff, J; McDuffie, JR; Reynolds, JC; Salaita, CG; Sebring, NG; Yanovski, JA, 2011)
"Comparing the effects of metformin or orlistat on hormone, lipid profile and ovulation status in obese women with polycystic ovary syndrome."9.15The effects of metformin or orlistat on obese women with polycystic ovary syndrome: a prospective randomized open-label study. ( Aflatoonian, A; Ghandi, S; Moghaddam, MH; Tabibnejad, N, 2011)
"The aim of this study was to evaluate the effect of exenatide compared to glimepiride on body weight, glycemic control and insulin resistance in type 2 diabetic patients taking metformin."9.15Exenatide or glimepiride added to metformin on metabolic control and on insulin resistance in type 2 diabetic patients. ( Bonaventura, A; Bossi, AC; Derosa, G; Fogari, E; Franzetti, IG; Guazzini, B; Maffioli, P; Putignano, P; Querci, F; Testori, G, 2011)
" Pioglitazone treatment (n = 10) reduced hepatic fat as assessed by magnetic resonance spectroscopy, despite a significant increase in body weight (Δ = 3."9.15Exenatide decreases hepatic fibroblast growth factor 21 resistance in non-alcoholic fatty liver disease in a mouse model of obesity and in a randomised controlled trial. ( Bajaj, M; Chan, L; Gonzalez, EV; Gutierrez, A; Jogi, M; Krishnamurthy, R; Muthupillai, R; Samson, SL; Sathyanarayana, P, 2011)
"The presence of fatty liver per ultrasound and liver-associated enzymes were measured in a select cohort of youth with both obesity and insulin resistance, and the effect of metformin on these parameters evaluated."9.14Treatment of non-alcoholic fatty liver disease with metformin versus lifestyle intervention in insulin-resistant adolescents. ( Ehlers, LB; Love-Osborne, K; Nadeau, KJ; Zeitler, PS, 2009)
"The aim of this study was to investigate the effects of pioglitazone or metformin on bone mass and atherosclerosis in patients with type 2 diabetes."9.14Baseline atherosclerosis parameter could assess the risk of bone loss during pioglitazone treatment in type 2 diabetes mellitus. ( Kanazawa, I; Kurioka, S; Sugimoto, T; Yamaguchi, T; Yamamoto, M; Yamauchi, M; Yano, S, 2010)
"Vildagliptin add-on has similar efficacy to glimepiride after 2 years' treatment, with markedly reduced hypoglycaemia risk and no weight gain."9.14Vildagliptin add-on to metformin produces similar efficacy and reduced hypoglycaemic risk compared with glimepiride, with no weight gain: results from a 2-year study. ( Ahren, B; Couturier, A; Dejager, S; Ferrannini, E; Foley, JE; Fonseca, V; Matthews, DR; Zinman, B, 2010)
"One hundred forty-two nondiabetic women with polycystic ovary syndrome (PCOS) who had at least one live-birth (LB) pregnancy on metformin diet (172 pregnancies, 180 LBs)."9.13Prevention of gestational diabetes by metformin plus diet in patients with polycystic ovary syndrome. ( Aregawi, D; Glueck, CJ; Pranikoff, J; Wang, P, 2008)
"We evaluated exenatide (EX) and metformin (MET), alone and in combination (COM), on menstrual cyclicity, hormonal parameters, metabolic profiles, and inflammatory markers in overweight, insulin-resistant women with PCOS."9.13Comparison of single and combined treatment with exenatide and metformin on menstrual cyclicity in overweight women with polycystic ovary syndrome. ( Bhushan, M; Bhushan, R; Elkind-Hirsch, K; Marrioneaux, O; Vernor, D, 2008)
"The present study aimed to investigate the effects of metformin on body weight in polycystic ovary syndrome (PCOS) patients by model-based meta-analysis (MBMA)."9.12Effects of metformin on body weight in polycystic ovary syndrome patients: model-based meta-analysis. ( Chen, X; He, S; Wang, D, 2021)
"This study was designed to assess the usefulness of a model-based index of insulin sensitivity during an oral glucose tolerance test (OGTT) in the identification of possible changes in this metabolic parameter produced by pharmacological agents known to be potent insulin sensitizers, that is metformin (M) and thiazolidinedione (T)."9.12Insulin sensitivity during oral glucose tolerance test and its relations to parameters of glucose metabolism and endothelial function in type 2 diabetic subjects under metformin and thiazolidinedione. ( Hanusch-Enserer, U; Kautzky-Willer, A; Ludvik, B; Pacini, G; Prager, R; Tura, A; Wagner, OF; Winzer, C, 2006)
"The authors hypothesized that a metformin (MET)-diet would improve symptoms of idiopathic intracranial hypertension (IIH) in women who also had polycystic ovary syndrome (PCOS) or hyperinsulinemia without PCOS."9.12Changes in weight, papilledema, headache, visual field, and life status in response to diet and metformin in women with idiopathic intracranial hypertension with and without concurrent polycystic ovary syndrome or hyperinsulinemia. ( Aregawi, D; Glueck, CJ; Goldenberg, N; Golnik, KC; Sieve, L; Wang, P, 2006)
"Metformin may safely assist olanzapine-treated patients in body weight and carbohydrate metabolism control."9.12Metformin as an adjunctive treatment to control body weight and metabolic dysfunction during olanzapine administration: a multicentric, double-blind, placebo-controlled trial. ( Baptista, T; Beaulieu, S; Carrizo, E; Connell, L; Dávila, A; de Baptista, EA; El Fakih, Y; Fernández, V; Galeazzi, T; Gutiérrez, MA; Rangel, N; Serrano, A; Servigna, M; Uzcátegui, E; Uzcátegui, M, 2007)
"The objective of the study was to evaluate the effects of metformin suspension on insulin sensitivity in PCOS patients."9.12Insulin sensitivity after metformin suspension in normal-weight women with polycystic ovary syndrome. ( De Feo, P; Falbo, A; Manguso, F; Orio, F; Palomba, S; Russo, T; Tolino, A; Zullo, F, 2007)
"65 kg/m(2)) hirsute women with polycystic ovary syndrome and normal insulin sensitivity were treated with 850 mg metformin orally, three times daily, for 4 months."9.12Metformin in normal-weight hirsute women with polycystic ovary syndrome with normal insulin sensitivity. ( Baracat, EC; Halpern, A; Maciel, GA; Marcondes, JA; Yamashita, SA, 2007)
"Our aim was to assess the effects of metformin on menstrual frequency, fasting plasma glucose (FPG), insulin resistance assessed as HOMA-index, weight, waist/hip ratio, blood pressure (BP), serum lipids, and testosterone levels in women with polycystic ovary syndrome (PCOS) METHODS: In a randomized, controlled, double-blinded setup, 56 women aged 18-45 with PCOS were treated with either metformin 850 mg or placebo twice daily for 6 months."9.12Efficacy of metformin in obese and non-obese women with polycystic ovary syndrome: a randomized, double-blinded, placebo-controlled cross-over trial. ( Flyvbjerg, A; Kesmodel, U; Lauszus, FF; Trolle, B, 2007)
" Objective To prospectively evaluate if administration of metformin to obese, diabetic patients with primary hypothyroidism on stable thyroxine replacement doses modifies TSH levels."9.12Metformin reduces thyrotropin levels in obese, diabetic women with primary hypothyroidism on thyroxine replacement therapy. ( Cordido, F; Isidro, ML; Nemiña, R; Penín, MA, 2007)
"To determine the clinical, hormonal, and biochemical effects of metformin therapy in obese and nonobese patients with polycystic ovary syndrome (PCOS)."9.11Nonobese women with polycystic ovary syndrome respond better than obese women to treatment with metformin. ( Abi Haidar, M; Alves da Motta, EL; Baracat, EC; de Lima, GR; Maciel, GA; Soares Júnior, JM, 2004)
"In a prospective observational study of 42 pregnancies in 39 Caucasian women (age 30 +/- 4 years) with polycystic ovary syndrome (PCOS), we examined effects of metformin on maternal insulin, insulin resistance (IR), insulin secretion (IS), weight gain, development of gestational diabetes (GD), testosterone and plasminogen activator inhibitor activity."9.11Metformin during pregnancy reduces insulin, insulin resistance, insulin secretion, weight, testosterone and development of gestational diabetes: prospective longitudinal assessment of women with polycystic ovary syndrome from preconception throughout preg ( Glueck, CJ; Goldenberg, N; Loftspring, M; Sherman, A; Wang, P, 2004)
"We prospectively assessed growth and motor-social development during the first 18 months of life in 126 live births (122 pregnancies) to 109 women with polycystic ovary syndrome (PCOS) who conceived on and continued metformin (1."9.11Height, weight, and motor-social development during the first 18 months of life in 126 infants born to 109 mothers with polycystic ovary syndrome who conceived on and continued metformin through pregnancy. ( Glueck, CJ; Goldenberg, N; Loftspring, M; Pranikoff, J; Sieve, L; Wang, P, 2004)
" metformin on the hormonal and biochemical features of patients with polycystic ovarian syndrome (PCOS)."9.11Orlistat is as beneficial as metformin in the treatment of polycystic ovarian syndrome. ( Atkin, SL; Holding, S; Jayagopal, V; Jennings, PE; Kilpatrick, ES, 2005)
" Although long-term treatment with metformin can increase Hcy levels in patients with type II diabetes mellitus or coronary heart disease, it is becoming an increasingly accepted and widespread medication in polycystic ovary syndrome (PCOS)."9.11Homocysteine levels in women with polycystic ovary syndrome treated with metformin versus rosiglitazone: a randomized study. ( Aslan, E; Bagis, T; Erkanli, S; Haydardedeoglu, B; Kilicdag, EB; Tarim, E; Zeyneloglu, HB, 2005)
"The aim of the current study was to assess the effects of B-group vitamins and folic acid administration on serum levels of homocysteine (Hcy) in patients with polycystic ovarian syndrome (PCOS) on short-term metformin treatment."9.11Administration of B-group vitamins reduces circulating homocysteine in polycystic ovarian syndrome patients treated with metformin: a randomized trial. ( Aslan, E; Bagis, T; Erkanli, S; Haydardedeoglu, B; Kilicdag, EB; Kuscu, E; Simsek, E; Tarim, E, 2005)
" The aim of this study was to assess the effects of rosiglitazone and metformin on cardiovascular disease risk factors such as insulin resistance, oxidative stress and homocysteine levels in lean patients with polycystic ovary syndrome (PCOS)."9.11The effects of rosiglitazone and metformin on oxidative stress and homocysteine levels in lean patients with polycystic ovary syndrome. ( Arslan, M; Ayvaz, G; Bukan, N; Cakir, N; Karakoç, A; Törüner, F; Yilmaz, M, 2005)
" There was a significant improvement in hirsutism at the end of the metformin phase compared with placebo: F-G score 15."9.10The effect of metformin on hirsutism in polycystic ovary syndrome. ( Gordon, D; Kelly, CJ, 2002)
"The results of this study confirm that sibutramine, orlistat and metformin are all effective and safe medications that reduce cardiovascular risk and can decrease the risk of type 2 diabetes mellitus in obese females."9.10Evaluation of the safety and efficacy of sibutramine, orlistat and metformin in the treatment of obesity. ( BascilTutuncu, N; Gokcel, A; Gumurdulu, Y; Guvener, N; Karakose, H; Melek Ertorer, E; Tanaci, N, 2002)
"To assess the effect of metformin on insulin sensitivity, glucose tolerance and components of the metabolic syndrome in patients with impaired glucose tolerance (IGT)."9.09Metabolic effects of metformin in patients with impaired glucose tolerance. ( Eriksson, JG; Forsén, B; Groop, L; Gullström, M; Häggblom, M; Lehtovirta, M; Taskinen, MR, 2001)
"Metformin lowered the LDL/HDL-cholesterol ratio by 12 and 6% at weeks 4 and 12, respectively, and reduced body weight by 1."9.08Metformin improves blood lipid pattern in nondiabetic patients with coronary heart disease. ( Bjerve, KS; Carlsen, SM; Følling, I; Rossvoll, O, 1996)
" Liraglutide is a glucagon-like peptide-1 receptor agonist that promotes sustained weight loss, as well as abdominal fat reduction, in individuals with obesity, prediabetes, and type 2 diabetes mellitus."9.05Liraglutide: New Perspectives for the Treatment of Polycystic Ovary Syndrome. ( Constantinidou, KG; Filippou, PK; Papaetis, GS; Stylianou, CS, 2020)
"We aimed to perform a meta-analysis of placebo-controlled studies investigating the body weight changes upon metformin treatment in participants older than 60 years."8.98Metformin induces significant reduction of body weight, total cholesterol and LDL levels in the elderly - A meta-analysis. ( Balaskó, M; Bérczi, B; Czopf, L; Garami, A; Gyöngyi, Z; Hartmann, P; Hegyi, P; Hussain, A; Ivic, I; Mátrai, P; Pétervári, E; Pótó, L; Sarlós, P; Simon, M; Solymár, M, 2018)
"In September 2018, we searched PubMed, Embase, and the Cochrane Library for studies published in English using the keywords metformin, obesity/overweight, and weight loss."8.98Efficacy of Metformin Treatment with Respect to Weight Reduction in Children and Adults with Obesity: A Systematic Review. ( Knibbe, CAJ; Lentferink, YE; van der Vorst, MMJ, 2018)
"We conducted a systematic-review and meta-analysis of metformin versus placebo for change in weight and metabolic syndrome for people on clozapine without diabetes mellitus."8.93Metformin for Clozapine Associated Obesity: A Systematic Review and Meta-Analysis. ( Kisely, S; Leung, J; Russell, AW; Siskind, DJ; Wysoczanski, D, 2016)
"Metformin, an oral anti-diabetic drug, is being considered increasingly for treatment and prevention of cancer, obesity as well as for the extension of healthy lifespan."8.88Metformin in obesity, cancer and aging: addressing controversies. ( Berstein, LM, 2012)
" While metformin has been shown to attenuate weight gain and insulin resistance, not all studies have shown a benefit in the reduction of antipsychotic-induced weight gain and insulin resistance."8.86The effect of metformin on anthropometrics and insulin resistance in patients receiving atypical antipsychotic agents: a meta-analysis. ( Coleman, CI; Ehret, M; Goethe, J; Lanosa, M, 2010)
"To assess the effectiveness of metformin in improving clinical and biochemical features of polycystic ovary syndrome."8.82Metformin in polycystic ovary syndrome: systematic review and meta-analysis. ( Flight, IH; Lord, JM; Norman, RJ, 2003)
"Metformin has become an established treatment for women with polycystic ovary syndrome, although controversy remains as to how effective it is and in which populations it should be used."8.82Metformin in polycystic ovary syndrome. ( Lord, J; Wilkin, T, 2004)
"Metformin, the most widely prescribed medication for obesity-associated type 2 diabetes (T2D), lowers plasma glucose levels, food intake, and body weight in rodents and humans, but the mechanistic site(s) of action remain elusive."8.31Metformin triggers a kidney GDF15-dependent area postrema axis to regulate food intake and body weight. ( Barros, DR; Bruce, K; Cherney, DZ; Chiu, JFM; Danaei, Z; Kuah, R; Lam, TKT; Li, RJW; Lim, YM; Mariani, LH; Reich, HN; Zhang, SY, 2023)
"We compared the efficacy and safety of beinaglutide, a glucagon-like peptide-1 (GLP-1) analogue with metformin in lowering the bodyweight of patients who were overweight/obese and non-diabetic."8.12Comparison of Beinaglutide Versus Metformin for Weight Loss in Overweight and Obese Non-diabetic Patients. ( Bi, Y; Feng, W; Fu, Y; Gao, L; Huang, H; Zhang, L; Zhang, N; Zhu, D, 2022)
"T2DM patients that performed regular exercise, had normal renal function and were receiving metformin were more likely to have clinically meaningful body weight reduction after one year treatment with dapagliflozin."8.12Predictors for successful weight reduction during treatment with Dapagliflozin among patients with type 2 diabetes mellitus in primary care. ( Huh, Y; Kim, YS, 2022)
"Linagliptin and its combination with metformin successfully ameliorated diabetic osteoporosis in HFD-fed mice possibly through modulation of BMP-2 and sclerostin."8.12Linagliptin in Combination With Metformin Ameliorates Diabetic Osteoporosis Through Modulating BMP-2 and Sclerostin in the High-Fat Diet Fed C57BL/6 Mice. ( Nirwan, N; Vohora, D, 2022)
" After metformin and exenatide supplementation, body weight, chow intake and ovarian morphology were observed."8.02Metformin and exenatide upregulate hepatocyte nuclear factor-4α, sex hormone binding globulin levels and improve hepatic triglyceride deposition in polycystic ovary syndrome with insulin resistance rats. ( He, B; Li, X; Lv, B; Wang, D; Xing, C; Zhao, H, 2021)
"The present study evaluated the effects of dapagliflozin, a SGLT2 inhibitor, or dapagliflozin plus metformin versus metformin monotherapy in patients with metabolic syndrome."8.02Dapagliflozin, metformin, monotherapy or both in patients with metabolic syndrome. ( Cheng, L; Fan, Y; Fu, Q; Lin, W; Liu, F; Wu, X; Zhang, X; Zhou, L, 2021)
" Metformin has potential effects on improving asthma airway inflammation."8.02Metformin alleviates allergic airway inflammation and increases Treg cells in obese asthma. ( Chen, M; Guo, Y; Hong, L; Jiang, S; Liu, S; Shi, J; Wang, Q; Yuan, X, 2021)
"To explore the effects of second-line combination therapies with metformin on body weight, HbA1c and health-related quality of life, as well as the risks of hypoglycaemia and further treatment intensification in the DISCOVER study, a 3-year, prospective, global observational study of patients with type 2 diabetes initiating second-line glucose-lowering therapy."8.02Associations between second-line glucose-lowering combination therapies with metformin and HbA1c, body weight, quality of life, hypoglycaemic events and glucose-lowering treatment intensification: The DISCOVER study. ( Charbonnel, B; Chen, H; Cooper, A; Gomes, MB; Ji, L; Khunti, K; Leigh, P; Nicolucci, A; Rathmann, W; Shestakova, MV; Siddiqui, A; Tang, F; Watada, H, 2021)
" Because previous data suggest the procognitive potential of the antidiabetic drug metformin, this study aimed to assess the effects of chronic clozapine and metformin oral administration (alone and in combination) on locomotor and exploratory activities and cognitive function in a reward-based test in control and a schizophrenia-like animal model (Wisket rats)."8.02Interaction of clozapine with metformin in a schizophrenia rat model. ( Adlan, LG; Benyhe, S; Büki, A; Heni, HE; Horvath, G; Kekesi, G; Kis, G; Szűcs, E, 2021)
"Metformin has been reported to decrease insulin resistance and is associated with a lower risk of pregnancy-induced hypertension and preeclampsia."7.91Effect of Metformin on a Preeclampsia-Like Mouse Model Induced by High-Fat Diet. ( Cao, G; Cao, X; Li, L; Wang, F; Yi, W, 2019)
"This study evaluated the preventative effects of metformin (Met) on glucocorticoid (GC)-induced osteoporosis in a rat model, compared with alendronate (Aln)."7.91Preventative effects of metformin on glucocorticoid-induced osteoporosis in rats. ( Li, Q; Li, Y; Meng, Y; Shi, D; Zhang, H; Zhao, J; Zuo, L, 2019)
"In diet-induced obesity, metformin (MF) has weight-lowering effect and improves glucose homeostasis and insulin sensitivity."7.91The evidence of metabolic-improving effect of metformin in Ay/a mice with genetically-induced melanocortin obesity and the contribution of hypothalamic mechanisms to this effect. ( Bakhtyukov, A; Bayunova, L; Derkach, K; Romanova, I; Shpakov, A; Zakharova, I; Zorina, I, 2019)
"Metformin treatment did not affect food intake, body weight, and casual blood glucose levels within each mouse line during the 20-week feeding period."7.91Metformin Attenuates Early-Stage Atherosclerosis in Mildly Hyperglycemic Oikawa-Nagao Mice. ( Asai, A; Kawahara, M; Miyazawa, T; Nagao, M; Oikawa, S; Shuto, Y; Sugihara, H, 2019)
"Metformin or/and α-LA attenuated the severity of the DSS-induced colitis through improving the reductions in body weights, the DAI, the colonic oxidative stress markers, TNF-α, and NF-κB levels, and the morphological mucosal damage scores."7.88New insights on the modulatory roles of metformin or alpha-lipoic acid versus their combination in dextran sulfate sodium-induced chronic colitis in rats. ( Elaidy, SM; Essawy, SS; Hassan, MS; Samman, FS, 2018)
"These data suggest that metformin protects against bleomycin-induced pulmonary fibrosis through activation of AMPK and amelioration of TGF-β signaling pathways."7.88Metformin alleviates bleomycin-induced pulmonary fibrosis in rats: Pharmacological effects and molecular mechanisms. ( Arava, S; Arya, DS; Bhatia, J; Gamad, N; Malik, S; Suchal, K; Tomar, A; Vasisht, S, 2018)
" Ursolic acid, metformin, gliclazide and their combinations when administered daily for 30 days significantly improved insulin sensitivity apart from behavioral and biochemical alterations in stressed mice."7.88Synergistic action of ursolic acid and metformin in experimental model of insulin resistance and related behavioral alterations. ( Ahuja, S; Akhtar, A; Kumar, A; Mourya, A; Sah, SP, 2018)
" In the present study, we investigated the potential therapeutic effects of metformin (Met) and saxagliptin (Saxa), as insulin sensitizing agents, in a rat model of brain aging and AD using D-galactose (D-gal, 150 mg/kg/day, s."7.85Involvement of insulin resistance in D-galactose-induced age-related dementia in rats: Protective role of metformin and saxagliptin. ( Attia, A; El-Shenawy, S; Gomaa, N; Hassan, A; Hegazy, R; Kenawy, S; Zaki, H, 2017)
" We evaluated whether obesity exacerbates progression of endometrial hyperplasia (EH) using the PRCre/+ PTENflox/+ mouse model and examined if the type 2 diabetes drug, metformin, could prevent EH."7.85Lean Body Weight and Metformin Are Insufficient to Prevent Endometrial Hyperplasia in Mice Harboring Inactivating Mutations in PTEN. ( Celestino, J; Iglesias, DA; Lu, KH; Schmandt, RE; Sun, CC; Yates, MS; Zhang, Q, 2017)
" In the present study, the effects of metformin on the development and recurrence of hepatocellular carcinoma (HCC) were investigated using the diethylnitrosamine (DEN)‑induced rat model of HCC."7.83Metformin inhibits early stage diethylnitrosamine‑induced hepatocarcinogenesis in rats. ( Chang, M; Choi, HJ; Jang, JJ; Jang, S; Jo, W; Lee, HJ; Park, HK; Ryu, JE; Son, WC; Yu, ES, 2016)
"Canagliflozin 100 and 300 mg provided sustained reductions in body weight, BMI, and waist circumference in a greater proportion of patients with T2DM versus glimepiride or placebo over 104 weeks."7.83Effects of canagliflozin on body weight and body composition in patients with type 2 diabetes over 104 weeks. ( Blonde, L; Canovatchel, W; Fung, A; Meininger, G; Stenlöf, K; Xie, J, 2016)
"To investigate changes in body weight trajectories after the addition of individual sulphonylureas (SUs) to metformin in patients with type 2 diabetes."7.83Addition of sulphonylurea to metformin does not relevantly change body weight: a prospective observational cohort study (ZODIAC-39). ( Bilo, HJ; de Bock, GH; Groenier, KH; Houweling, ST; Kleefstra, N; Landman, GW; Schrijnders, D; van Hateren, KJ; Wever, R, 2016)
"We investigated the effects of metformin and celecoxib on obesity-induced adipose tissue inflammation, insulin resistance (IR), fatty liver, and high blood pressure in high-fat (HF) fed rats."7.83Additional effect of metformin and celecoxib against lipid dysregulation and adipose tissue inflammation in high-fat fed rats with insulin resistance and fatty liver. ( Hsieh, PS; Hung, YJ; Lu, CH, 2016)
" This study is to investigate the role of apoA5 in obesity-associated hypertriglyceridemia and metformin-related hypotriglyceridemic actions."7.83Metformin ameliorates obesity-associated hypertriglyceridemia in mice partly through the apolipoprotein A5 pathway. ( Chen, LZ; Huang, XS; Li, R; Zhao, SP; Zhao, W, 2016)
" In a post hoc meta-analysis of combined data from the 2 studies (n = 124), there was considerable overlapping in AUC(infinity) values between gender and race (Caucasians, Blacks, and Hispanics), making neither gender- nor racial-based dosing of pioglitazone or metformin necessary."7.82Oral antidiabetic drugs: bioavailability assessment of fixed-dose combination tablets of pioglitazone and metformin. Effect of body weight, gender, and race on systemic exposures of each drug. ( Bradford, D; Cao, C; Karim, A; Laurent, A; Schwartz, L; Slater, M; Zhao, Z, 2007)
"To determine the effects of metformin therapy in children with metabolic syndrome (MS)."7.81Metformin treatment improves weight and dyslipidemia in children with metabolic syndrome. ( Ashraf, AP; Luong, DQ; Oster, R, 2015)
" We hypothesized that neonatal treatment with antidiabetic drug biguanide metformin would positively modify regulation of growth hormone--IGF-1--insulin signaling pathway slowing down aging and improving cancer preventive patterns in rodents."7.81Sex differences in aging, life span and spontaneous tumorigenesis in 129/Sv mice neonatally exposed to metformin. ( Anisimov, VN; Egormin, PA; Khaitsev, NV; Panchenko, AV; Popovich, IG; Semenchenko, AV; Trashkov, AP; Tyndyk, ML; Vasiliev, AG; Yurova, MN; Zabezhinski, MA, 2015)
" Metformin is a first-line treatment of type 2 diabetes, with minimal weight loss in humans."7.81Synergistic Effects of a GPR119 Agonist with Metformin on Weight Loss in Diet-Induced Obese Mice. ( Al-Barazanji, K; Benson, W; Binz, J; Chen, L; Generaux, C; McNulty, J; Young, A, 2015)
"Sixty six adult patients with schizophrenia or schizoaffective disorder treated, with atypical antipsychotics, and who had increased by more than 10% their pre treatment body weight, were randomly assigned to receive metformin or placebo in a double-blind study."7.81Metformin for treatment of antipsychotic-induced weight gain in a South Asian population with schizophrenia or schizoaffective disorder: A double blind, randomized, placebo controlled study. ( Dayabandara, M; de Silva, VA; Gunewardena, H; Hanwella, R; Henegama, T; Suraweera, C; Wijesundara, H, 2015)
"Metformin decreases polycystic ovary syndrome (PCOS) symptoms, induces ovulation, and may improve developmental competence of in vitro oocyte maturation."7.81Does metformin improve in vitro maturation and ultrastructure of oocytes retrieved from estradiol valerate polycystic ovary syndrome-induced rats. ( Mesbah, F; Mirkhani, H; Moslem, M; Vojdani, Z, 2015)
"The aim of our study was to assess the value of blood pressure and heart rate using the 24-hour blood pressure monitoring (ABPM) before and after treatment with metformin to patients with polycystic ovary syndrome (PCOS) and normal lean."7.81[Metformin and changes in blood pressure and heart rate in lean patients with polycystic ovary syndrome (PCOS)--preliminary study]. ( Kiałka, M; Klocek, M; Kowalczuk, A; Migacz, K; Milewicz, T; Ociepka, A; Tomczyk, R, 2015)
"In the present study, the ability of metformin to inhibit skin tumor promotion by 12-O-tetradecanoylphorbol-13-acetate (TPA) was analyzed in mice maintained on either an overweight control diet or an obesity-inducing diet."7.80Metformin inhibits skin tumor promotion in overweight and obese mice. ( Angel, JM; Beltran, L; Blando, J; Checkley, LA; Cho, J; DiGiovanni, J; Hursting, SD; Rho, O, 2014)
"Elevated asymmetric dimethylarginine (ADMA) levels and nitric oxide (NO) deficiency are associated with the development of hypertension."7.80Metformin reduces asymmetric dimethylarginine and prevents hypertension in spontaneously hypertensive rats. ( Hsu, CN; Huang, LT; Kuo, HC; Tain, YL; Tsai, CM, 2014)
"Metformin administration resulted in significant decrease in the body weight, body mass index, hirsutism score, fasting and postprandial blood glucose, fasting serum insulin, HOMA index, sleep disturbances scale, and Epworth sleepiness scale compared to the untreated PCOS group."7.80Effect of metformin on sleep disorders in adolescent girls with polycystic ovarian syndrome. ( Abdelmotaleb, GS; Aly, MK; El-Sharkawy, AA; Kabel, AM, 2014)
" At the end of the feeding schedule, Dia group had insulin resistance along with increased blood glucose, triglyceride, uric acid and nitric oxide (NO) levels."7.78Attenuation of insulin resistance, metabolic syndrome and hepatic oxidative stress by resveratrol in fructose-fed rats. ( Bagul, PK; Banerjee, SK; Bastia, T; Chakravarty, S; Madhusudana, K; Matapally, S; Middela, H; Padiya, R; Reddy, BR, 2012)
" We hypothesised that intervention with metformin would diminish the HF-feeding-evoked cognitive deficit by improving insulin sensitivity."7.78A high-fat-diet-induced cognitive deficit in rats that is not prevented by improving insulin sensitivity with metformin. ( Balfour, DJ; McNeilly, AD; Stewart, CA; Sutherland, C; Williamson, R, 2012)
"To define the pharmacogenetic features of the effect of metformin in coronary heart disease (CHD) patients with metabolic syndrome (MS) or type 2 diabetes mellitus (T2DM), by taking into consideration PPAR-gamma2 Pro1 2Ala polymorphism."7.78[Pharmacogenetic features of the effect of metformin in patients with coronary heart disease in the presence of metabolic syndrome and type 2 diabetes mellitus in terms of PPAR-gamma2 gene polymorphism]. ( Kaĭdashev, IP; Kutsenko, LA; Lavrenko, AV; Mamontova, TV; Shlykova, OA, 2012)
" The chronic treatment of inbred 129/Sv mice with metformin (100 mg/kg in drinking water) slightly modified the food consumption but failed to influence the dynamics of body weight, decreased by 13."7.76Gender differences in metformin effect on aging, life span and spontaneous tumorigenesis in 129/Sv mice. ( Anisimov, VN; Berstein, LM; Egormin, PA; Kovalenko, IG; Piskunova, TS; Popovich, IG; Poroshina, TE; Rosenfeld, SV; Semenchenko, AV; Tyndyk, ML; Yurova, MV; Zabezhinski, MA, 2010)
"Women with GDM treated with metformin and with similar baseline risk factors for adverse pregnancy outcomes had less weight gain and improved neonatal outcomes compared with those treated with insulin."7.75Pregnancy outcomes in women with gestational diabetes treated with metformin or insulin: a case-control study. ( Balani, J; Hyer, SL; Rodin, DA; Shehata, H, 2009)
" Here we show the chronic treatment of female outbred SHR mice with metformin (100 mg/kg in drinking water) slightly modified the food consumption but decreased the body weight after the age of 20 months, slowed down the age-related switch-off of estrous function, increased mean life span by 37."7.74Metformin slows down aging and extends life span of female SHR mice. ( Anisimov, VN; Berstein, LM; Egormin, PA; Kovalenko, IG; Piskunova, TS; Popovich, IG; Poroshina, TE; Semenchenko, AV; Tyndyk, ML; Yurova, MV; Zabezhinski, MA, 2008)
"The effect of 6 months of metformin treatment was prospectively assessed in 188 PCOS patients, divided into three groups according to body mass index (BMI; lean: BMI<25 kg/m2, overweight: BMI 25-29 kg/m2, and obese: BMI30 kg/m2)."7.74Metformin improves polycystic ovary syndrome symptoms irrespective of pre-treatment insulin resistance. ( Benson, S; Dietz, T; Elsenbruch, S; Hahn, S; Janssen, OE; Kimmig, R; Lahner, H; Mann, K; Moeller, LC; Schmidt, M; Tan, S, 2007)
"55 g/d for 28 weeks) would ameliorate morbid obesity and reduce centripetal obesity; lipid and lipoprotein cholesterol, insulin, and leptin levels; and plasminogen activator inhibitor activity (PAI-Fx), risk factors for coronary heart disease (CHD)."7.71Metformin reduces weight, centripetal obesity, insulin, leptin, and low-density lipoprotein cholesterol in nondiabetic, morbidly obese subjects with body mass index greater than 30. ( Fontaine, RN; Glueck, CJ; Illig, E; Lang, JE; McCullough, P; Sieve-Smith, L; Streicher, P; Subbiah, MT; Tracy, TM; Wang, P; Weber, K, 2001)
"To evaluate the long-term effects of metformin on biochemical variables and body weight in polycystic ovary syndrome (PCOS)."7.71Biochemical and body weight changes with metformin in polycystic ovary syndrome. ( Batukan, C; Batukan, M; Baysal, B, 2001)
"Before metformin therapy, after covariance adjustment for age, the two cohorts did not differ in height, weight, basal metabolic index, insulin, insulin resistance, or insulin secretion."7.71Metformin therapy throughout pregnancy reduces the development of gestational diabetes in women with polycystic ovary syndrome. ( Glueck, CJ; Kobayashi, S; Phillips, H; Sieve-Smith, L; Wang, P, 2002)
"HCl and metformin on diabetes and obesity were investigated in Wistar fatty rats, which are hyperglycaemic and hypertriglyceridaemic and have higher plasma levels of total ketone bodies than lean rats."7.71Effects of combined pioglitazone and metformin on diabetes and obesity in Wistar fatty rats. ( Ikeda, H; Odaka, H; Sugiyama, Y; Suzuki, M; Suzuki, N, 2002)
"To determine whether improvement of insulin resistance decreases blood pressure as well as obesity, metformin (100 mg/kg/d) or vehicle was administered for 20 weeks to 12-week-old male Otsuka Long-Evans Tokushima Fatty (OLETF) rats (n = 10 each), a newly developed animal model of non-insulin-dependent diabetes mellitus (NIDDM) with mild obesity, hyperinsulinemia, and hypertriglyceridemia."7.69Metformin decreases blood pressure and obesity in OLETF rats via improvement of insulin resistance. ( Inukai, K; Ishii, J; Kashiwabara, H; Katayama, S; Kikuchi, C; Kosegawa, I; Negishi, K; Oka, Y, 1996)
"Type 2 diabetes mellitus is closely related to nonalcoholic fatty liver disease(NAFLD)."6.94Liraglutide or insulin glargine treatments improves hepatic fat in obese patients with type 2 diabetes and nonalcoholic fatty liver disease in twenty-six weeks: A randomized placebo-controlled trial. ( Guo, W; Lin, L; Tian, W; Xu, X, 2020)
"Prediabetes is associated with increased prevalence of cardiovascular disease (CVD)."6.87Effect of intensive lifestyle modification & metformin on cardiovascular risk in prediabetes: A pilot randomized control trial. ( Bantwal, G; Fathima, S; George, B; Kulkarni, S; Umesh, S; Xavier, D, 2018)
"The objective of this study was to assess the efficacy and safety of metformin at the dosage of 2,500 mg/day in the treatment of obese women with PCOS and also to evaluate its effect on weight, hormones, and lipid profile."6.75Metformin 2,500 mg/day in the treatment of obese women with polycystic ovary syndrome and its effect on weight, hormones, and lipid profile. ( Aghahosseini, M; Aleyaseen, A; Kashani, L; Moddaress-Hashemi, S; Mofid, B; Safdarian, L, 2010)
"Liraglutide is a promising drug for the treatment of type 2 diabetes."6.72Five weeks of treatment with the GLP-1 analogue liraglutide improves glycaemic control and lowers body weight in subjects with type 2 diabetes. ( Filipczak, R; Gumprecht, J; Hompesch, M; Le, TD; Nauck, MA; Zdravkovic, M, 2006)
"However, many antidiabetic treatments increase body weight."6.44Metformin and body weight. ( Golay, A, 2008)
"Metformin is a commonly used drug of PCOS but few studies on whether metformin can improve the follicle development and ovarian function in PCOS."5.91Metformin improves polycystic ovary syndrome in mice by inhibiting ovarian ferroptosis. ( Chang, Q; Chen, X; He, R; Hei, C; Li, G; Liang, X; Liu, H; Liu, X; Ouyang, J; Peng, Q; Ren, S; Sun, M; Sun, Y; Wang, C; Wang, Q; Wu, X; Xie, H, 2023)
"Metformin is a widely used drug for treating type 2 diabetes and is also used for delaying sexual maturation in girls with precocious puberty."5.72Metformin treatment of juvenile mice alters aging-related developmental and metabolic phenotypes. ( Bartke, A; Fang, Y; Medina, D; Yuan, R; Zhu, Y, 2022)
"Janagliflozin 25 or 50 mg once-daily added to metformin therapy significantly improved glycaemic control, reduced body weight and systolic blood pressure, improved high-density lipoprotein cholesterol and insulin sensitivity, and was generally well-tolerated by Chinese T2D patients who had poor glycaemic control with metformin monotherapy."5.69Efficacy and safety of janagliflozin as add-on therapy to metformin in Chinese patients with type 2 diabetes inadequately controlled with metformin alone: A multicentre, randomized, double-blind, placebo-controlled, phase 3 trial. ( Chen, L; Chen, X; Cheng, Z; Gao, L; Guo, Y; Ji, L; Li, J; Liao, L; Pang, S; Song, W; Su, B; Su, X; Sun, J; Tan, X; Wang, K; Wang, Y; Xu, F; Ye, J, 2023)
"The Diabetes Prevention Program (DPP) and metformin can prevent or delay the onset of type 2 diabetes mellitus (T2DM) among patients with prediabetes."5.69Study protocol: Behavioral economics and self-determination theory to change diabetes risk (BEST Change). ( Carter, EW; Heisler, M; Herman, WH; Kim, HM; Kullgren, JT; McEwen, LN; Resnicow, K; Rogers, B; Stoll, S; Vadari, HS; Volpp, KG, 2023)
"In overweight or obese patients with T2DM, a once-weekly subcutaneous administration of PEG-Loxe for 16 weeks, in addition to lifestyle interventions or oral antidiabetic drug therapy, resulted in significantly greater weight loss compared to metformin."5.69Short-term effect of polyethylene glycol loxenatide on weight loss in overweight or obese patients with type 2 diabetes: An open-label, parallel-arm, randomized, metformin-controlled trial. ( Cai, H; Chen, Q; Duan, Y; Zhang, X; Zhao, Y, 2023)
"We aimed to determine the efficacy and safety of DDG combined with metformin for the treatment of T2DM patients with obesity."5.69Effectiveness and safety of Daixie Decoction granules combined with metformin for the treatment of T2DM patients with obesity: study protocol for a randomized, double-blinded, placebo-controlled, multicentre clinical trial. ( Liu, Z; Wang, F; Wang, L; Wang, M; Zhang, J; Zhang, K; Zhang, Y; Zhou, S; Zhou, Y, 2023)
"The sitagliptin group receiving empagliflozin saw a substantial drop in HbA1c, fasting and postprandial plasma glucose levels, body weight, and blood pressure compared to the starting point."5.69Adding empagliflozin to sitagliptin plus metformin vs. adding sitagliptin to empagliflozin plus metformin as triple therapy in Egyptian patients with type 2 diabetes: a 12-week open trial. ( Ali, AM; Mostafa, MAA; Rabea, H; Salem, HF; Zakaraia, HG, 2023)
"A rat model of PCOS-IR was established using a high-fat diet (49 d) combined with letrozole (1 mg/kg·d, for 28 d)."5.62Effects of total flavonoids from Eucommia ulmoides Oliv. leaves on polycystic ovary syndrome with insulin resistance model rats induced by letrozole combined with a high-fat diet. ( Li, CX; Li, M; Miao, MS; Peng, MF; Ren, Z; Song, YG; Tian, S, 2021)
"Metformin is an antidiabetic drug commonly used in obesity treatment."5.56Effect of high-fat diet-induced obesity on thyroid gland structure in female rats and the possible ameliorating effect of metformin therapy. ( El-Sayed, SM; Ibrahim, HM, 2020)
"Rats treated with metformin showed a significant improvement in the aforementioned parameters."5.56Combined treatments with metformin and phosphodiesterase inhibitors alleviate nonalcoholic fatty liver disease in high-fat diet fed rats: a comparative study. ( Abdel-Latif, RG; El-Deen, RM; Heeba, GH; Khalifa, MMA, 2020)
"Twelve weeks of treatment with metformin resulted in a significant reduction in body weight and improved insulin sensitivity, but IHTG content and FA oxidation remained unchanged."5.51Metformin maintains intrahepatic triglyceride content through increased hepatic de novo lipogenesis. ( Charlton, C; Cornfield, T; Green, CJ; Hazlehurst, JM; Hodson, L; Marjot, T; McCullagh, J; Moolla, A; Pinnick, KE; Tomlinson, JW; Walsby-Tickle, J; Westcott, F, 2022)
"Here we study whether circulating GDF-15 levels were raised by such metformin treatment and whether they related to changes in body weight and visceral fat in children with obesity."5.51A 24-month metformin treatment study of children with obesity: Changes in circulating GDF-15 and associations with changes in body weight and visceral fat. ( Bassols, J; Carreras-Badosa, G; de Zegher, F; Díaz-Roldán, F; Gómez-Vilarrubla, A; Ibañez, L; López-Bermejo, A; Martínez-Calcerrada, JM; Mas-Parés, B; Prats-Puig, A; Puerto-Carranza, E; Xargay-Torrent, S, 2022)
"Polycystic ovary syndrome is one of the most common causes of female infertility, affecting 5-10% of the population."5.51Ocimum kilimandscharicum L. restores ovarian functions in letrozole - induced Polycystic Ovary Syndrome (PCOS) in rats: Comparison with metformin. ( AbdelMaksoud, S; El-Bahy, AA; Handoussa, H; Khaled, N; Radwan, R, 2019)
"Men with type 2 diabetes (T2D) and obesity are often characterised by low testosterone (T)."5.48Short-term combined treatment with exenatide and metformin is superior to glimepiride combined metformin in improvement of serum testosterone levels in type 2 diabetic patients with obesity. ( Hao, M; Kuang, HY; Li, BW; Ma, XF; Pan, J; Shao, N; Wu, WH; Yu, XY; Yu, YM; Zhang, HJ, 2018)
"Metformin was treated daily for 14 weeks in a high-fat dieting C57BL/6J mice."5.43Metformin Prevents Fatty Liver and Improves Balance of White/Brown Adipose in an Obesity Mouse Model by Inducing FGF21. ( Byun, JK; Cho, ML; Choi, JY; Jeong, JH; Jhun, JY; Kim, EK; Kim, JK; Lee, SH; Lee, SY, 2016)
"Metformin (Met), which is an insulin-sensitizer, decreases insulin resistance and fasting insulin levels."5.42Intracerebroventricular metformin decreases body weight but has pro-oxidant effects and decreases survival. ( Brochier, AW; de Assis, AM; de Carvalho, AK; Gnoatto, J; Haas, CB; Hansel, G; Muller, AP; Oses, JP; Portela, LV; Zimmer, ER, 2015)
"The metformin treatment of Wistar rats with obesity induced by high-fat diet was carried out for 2 months (daily dose of 200 mg/kg)."5.42[THE EFFECTS OF LONG-TERM METFORMIN TREATMENT ON THE ACTIVITY OF ADENYLYL CYCLASE SYSTEM AND NO-SYNTHASES IN THE BRAIN AND THE MYOCARDIUM OF RATS WITH OBESITY]. ( Bondareva, VM; Derkach, KV; Ignatieva, PA; Kuznetsova, LA; Sharova, TS; Shpakov, AO, 2015)
" The results showed that compared to dual therapy with DPP-4 inhibitor add-on to metformin, triple therapy with SGLT-2 inhibitor add-on to DPP-4 inhibitor plus metformin was associated with greater reductions in HbA1c, fasting blood glucose, postprandial blood glucose, body weight, and blood pressure (P < ."5.41Efficacy and Safety of Triple Therapy with SGLT-2 Inhibitor, DPP-4 Inhibitor, and Metformin in Type 2 Diabetes: A Meta-Analysis. ( Li, M; Wang, S; Wang, X, 2023)
"In conclusion, the administration of once-weekly Semaglutide exhibited a substantial reduction in HbA1c, average systolic blood pressure (SBP), mean diastolic blood pressure (DBP), body weight, waist circumference, body mass index (BMI), and a rise in pulse rate, as opposed to the once-daily administration of Sitagliptin."5.41Comparative efficacy and safety profile of once-weekly Semaglutide versus once-daily Sitagliptin as an add-on to metformin in patients with type 2 diabetes: a systematic review and meta-analysis. ( Ahmed, M; Butt, TS; Ganesan, S; Khatri, M; Kumar, S; Madhurita, F; Nageeta, F; Patel, T; Sohail, R; Varrassi, G; Zafar, M; Zafar, W; Zaman, MU, 2023)
"The glucose-lowering drug metformin has recently been shown to reduce myocardial oxygen consumption and increase myocardial efficiency in chronic heart failure (HF) patients without diabetes."5.41Metformin Lowers Body Weight But Fails to Increase Insulin Sensitivity in Chronic Heart Failure Patients without Diabetes: a Randomized, Double-Blind, Placebo-Controlled Study. ( Brøsen, K; Bøtker, HE; Dollerup, OL; Frøkiær, J; Hansson, NH; Jespersen, NR; Jessen, N; Larsen, AH; Møller, N; Nørrelund, H; Wiggers, H, 2021)
"These data suggest that the beneficial effects of liraglutide and sitagliptin on glucose metabolism, body weight and bile acids, when used as add-on therapies to metformin or sulphonylureas, are not linked to changes in the intestinal microbiota (NCT01744236)."5.41Liraglutide and sitagliptin have no effect on intestinal microbiota composition: A 12-week randomized placebo-controlled trial in adults with type 2 diabetes. ( Belzer, C; Cahen, DL; Davids, M; de Vos, WM; Fluitman, KS; Groen, AK; Herrema, H; Kramer, MHH; Nieuwdorp, M; Smits, MM; van Raalte, DH, 2021)
"Both bortezomib and metformin have been proposed as potential therapeutics in TSC."5.38Therapeutic trial of metformin and bortezomib in a mouse model of tuberous sclerosis complex (TSC). ( Auricchio, N; Kwiatkowski, DJ; Malinowska, I; Manning, BD; Shaw, R, 2012)
"Insulin resistance has been shown to be associated with cardiac sympathovagal imbalance, myocardial dysfunction, and cardiac mitochondrial dysfunction."5.38Cardioprotective effects of metformin and vildagliptin in adult rats with insulin resistance induced by a high-fat diet. ( Apaijai, N; Chattipakorn, N; Chattipakorn, SC; Pintana, H, 2012)
"Advanced HF (heart failure) is associated with altered substrate metabolism."5.37Effect of metformin therapy on cardiac function and survival in a volume-overload model of heart failure in rats. ( Benada, O; Benes, J; Cervenka, L; Drahota, Z; Houstek, J; Kazdova, L; Kolar, M; Kopecky, J; Kovarova, N; Medrikova, D; Melenovsky, V; Petrak, J; Sedmera, D; Skaroupkova, P; Strnad, H; Vrbacky, M, 2011)
"Metformin treatment also improved hyperleptinemia, whereas pioglitazone was ineffective."5.36Metformin reduces body weight gain and improves glucose intolerance in high-fat diet-fed C57BL/6J mice. ( Hirasawa, Y; Ito, M; Kyuki, K; Matsui, Y; Sugiura, T; Toyoshi, T, 2010)
"There is no known treatment for fatty liver, a ubiquitous cause of chronic liver disease."5.31Metformin reverses fatty liver disease in obese, leptin-deficient mice. ( Chuckaree, C; Diehl, AM; Kuhajda, F; Lin, HZ; Ronnet, G; Yang, SQ, 2000)
"Metformin treatment (1000-2000 mg/day) over 6 months in pubertal children and/or adolescents with obesity and hyperinsulinism is associated with a reduction in body mass index (BMI) and the insulin resistance index (HOMA-IR)."5.30Effects of metformin administration on endocrine-metabolic parameters, visceral adiposity and cardiovascular risk factors in children with obesity and risk markers for metabolic syndrome: A pilot study. ( Bassols, J; Carreras-Badosa, G; de Zegher, F; Díaz-Roldán, F; Dorado-Ceballos, E; Ibáñez, L; López-Bermejo, A; Martínez-Calcerrada, JM; Mas-Parés, B; Osiniri, I; Prats-Puig, A; Xargay-Torrent, S, 2019)
"This study provides evidence that, compared to glimepiride, saxagliptin more effectively achieves a composite endpoint of adequate glycaemic control without hypoglycaemia and without weight gain in T2D patients who are inadequately controlled with metformin monotherapy, especially in overweight patients with moderate hyperglycaemia and a relatively short duration of diabetes."5.30Comparative effect of saxagliptin and glimepiride with a composite endpoint of adequate glycaemic control without hypoglycaemia and without weight gain in patients uncontrolled with metformin therapy: Results from the SPECIFY study, a 48-week, multi-centr ( Bi, Y; Cheng, J; Gu, T; Li, D; Ma, J; Shao, J; Shi, B; Sun, Z; Xu, L; Zhang, H; Zhang, Q; Zhong, S; Zhu, D; Zhu, L, 2019)
" The objective of this study was to evaluate the effects of a triple combination of leucine, metformin, and sildenafil (NS-0200) on body weight and obesity comorbidities in a phase 2 randomized trial."5.30Randomized Controlled Trial of a Leucine-Metformin-Sildenafil Combination (NS-0200) on Weight and Metabolic Parameters. ( Barritt, AS; Chalasani, N; Flores, O; Kolterman, O; Rinella, M; Siddiqui, M; Vuppalanchi, R; Zemel, MB, 2019)
"Metformin treatment significantly reduced LVMI, LVM, office systolic BP, body weight, and oxidative stress."5.30A randomized controlled trial of metformin on left ventricular hypertrophy in patients with coronary artery disease without diabetes: the MET-REMODEL trial. ( Al-Talabany, S; Baig, F; Bhalraam, U; Choy, AM; Gandy, SJ; George, J; Houston, JG; Hussain, MS; Khan, F; Lang, CC; Matthew, S; McKinnie, A; Mohan, M; Mordi, IR; Singh, JSS; Struthers, AD, 2019)
"Metformin-treated rats gained significantly less weight."5.29Prevention of hyperglycemia in the Zucker diabetic fatty rat by treatment with metformin or troglitazone. ( Burant, CF; Polonsky, KS; Pugh, W; Sreenan, S; Sturis, J, 1996)
"This post hoc analysis assessed the effects on cardiovascular risk factors of body weight, systolic blood pressure (SBP) and triglycerides after 28 weeks' treatment with exenatide once weekly plus dapagliflozin, as compared with exenatide once weekly or dapagliflozin, in patient subpopulations from the DURATION-8 trial of patients with type 2 diabetes mellitus (T2DM) inadequately controlled with metformin alone."5.27Effects of exenatide once weekly plus dapagliflozin, exenatide once weekly, or dapagliflozin, added to metformin monotherapy, on body weight, systolic blood pressure, and triglycerides in patients with type 2 diabetes in the DURATION-8 study. ( Ahmed, A; Frías, JP; Guja, C; Hardy, E; Jabbour, SA; Öhman, P, 2018)
" Although there is evidence for weight loss with metformin for people with obesity who are already taking clozapine, there have been no published trials that have investigated the effect of metformin in attenuating weight gain at the time of clozapine initiation."5.27CoMET: a protocol for a randomised controlled trial of co-commencement of METformin as an adjunctive treatment to attenuate weight gain and metabolic syndrome in patients with schizophrenia newly commenced on clozapine. ( Baker, A; Flaws, D; Friend, N; Kisely, S; Lim, C; McGrath, JJ; Moudgil, V; Patterson, S; Russell, A; Sardinha, S; Siskind, D; Stedman, T; Suetani, S; Winckel, K, 2018)
"Proof-of-concept study to investigate the amplifying effects of diazoxide (DZX)-mediated insulin suppression on lifestyle-induced weight loss in nondiabetic, hyperinsulinemic, obese men."5.27High-Dose, Diazoxide-Mediated Insulin Suppression Boosts Weight Loss Induced by Lifestyle Intervention. ( Brandon, T; de Boer, H; Filius, M; Hermus, A; Loves, S; Mekking, M; Tack, CJ; van Groningen, L, 2018)
"In Japanese patients with type 2 diabetes treated with vildagliptin and low-dose metformin, metformin up-titration significantly but modestly improved glycemic control without hypoglycemia and weight gain."5.24Safety and efficacy of metformin up-titration in Japanese patients with type 2 diabetes mellitus treated with vildagliptin and low-dose metformin. ( Azuma, K; Goto, H; Ikeda, F; Kanazawa, A; Komiya, K; Masuyama, A; Mita, T; Ogihara, T; Ohmura, C; Osonoi, T; Osonoi, Y; Saito, M; Sato, J; Shimizu, T; Someya, Y; Suzuki, L; Takayanagi, N; Takeno, K; Uzawa, H; Watada, H, 2017)
"Compared with glimepiride, Sita/Met as an initial treatment led to significantly greater improvements in glycemic control and body weight changes, with a lower incidence of hypoglycemia, over 30 weeks."5.24Efficacy and safety of sitagliptin/metformin fixed-dose combination compared with glimepiride in patients with type 2 diabetes: A multicenter randomized double-blind study. ( Chung, SC; Kim, IJ; Kim, SS; Kim, YI; Lee, KJ; Lee, SJ; Lee, YS; Park, JH, 2017)
"Steady-state population pharmacokinetics of a noncommercial immediate-release metformin (hydrochloride) drug product were characterized in 28 severely obese children with insulin resistance."5.24Effects of SLC22A1 Polymorphisms on Metformin-Induced Reductions in Adiposity and Metformin Pharmacokinetics in Obese Children With Insulin Resistance. ( Alfaro, RM; Calis, KA; Hon, YY; Reynolds, JC; Roza, O; Sam, WJ; Yanovski, JA, 2017)
"Liraglutide 3 mg was recently approved as an anti-obesity drug."5.24Short-term effectiveness of low dose liraglutide in combination with metformin versus high dose liraglutide alone in treatment of obese PCOS: randomized trial. ( Goričar, K; Janez, A; Jensterle, M; Kravos, NA, 2017)
"Compared with metformin, vildagliptin combined with metformin could significantly reduce FPG, HbA1c and body weight."5.22Efficacy and safety of combination therapy with vildagliptin and metformin vs. metformin monotherapy for Type 2 Diabetes Mellitus therapy: a meta-analysis. ( Cao, L; Ding, Y; Dong, F; Li, Y; Lin, M; Lin, S; Liu, Y; Qu, Y, 2022)
"Changes from baseline in HbA1c, body weight, and systolic blood pressure (BP) with canagliflozin 100 and 300 mg versus placebo or active comparator (i."5.22Efficacy and safety of canagliflozin in patients with type 2 diabetes mellitus from Latin America. ( Alba, M; Cerdas, S; Chacon, Mdel P; Eliaschewitz, FG; Lavalle-González, FJ; Tong, C, 2016)
"Dapagliflozin, a highly selective sodium-glucose cotransporter 2 inhibitor, reduces hyperglycemia, body weight, and blood pressure in patients with type 2 diabetes (T2D)."5.22Efficacy and safety of dapagliflozin in Asian patients with type 2 diabetes after metformin failure: A randomized controlled trial. ( Han, P; Iqbal, N; Johnsson, E; Mansfield, T; Min, KW; Ptaszynska, A; T'Joen, C; Wang, B; Yang, W, 2016)
" In this study, data were pooled from two randomized, placebo-controlled trials, which were originally designed to examine the efficacy of metformin in treating antipsychotic-induced weight gain and other metabolic abnormalities."5.22Metformin treatment of antipsychotic-induced dyslipidemia: an analysis of two randomized, placebo-controlled trials. ( Chan, PK; Gao, KM; Guo, WB; Jin, H; Ou, JJ; Shao, P; Wu, RR; Zhang, FY; Zhao, JP, 2016)
"Liraglutide provided better glycaemic control and greater body weight reduction than sitagliptin when administered as add-on to metformin."5.22Efficacy and safety of liraglutide versus sitagliptin, both in combination with metformin, in Chinese patients with type 2 diabetes: a 26-week, open-label, randomized, active comparator clinical trial. ( Bian, F; Bosch-Traberg, H; Geng, J; Li, Y; Liu, J; Liu, Y; Luo, Y; Lv, X; Mu, Y; Peng, Y; Sun, Y; Yang, J; Zang, L, 2016)
"Our results show that Metformin and acupuncture combined therapy significantly improves body weight, body mass index (BMI), fasting blood sugar (FBS), fasting insulin (FINS), homeostasis model assessment (HOMA) index, interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), leptin, adiponectin, glucagon-like peptide-1 (GLP-1), resistin, serotonin, free fatty acids (FFAs), triglyceride (TG), low-density lipoprotein cholesterol (LDLc), high-density lipoprotein cholesterol (HDLc) and ceramides."5.22Comparative evaluation of the therapeutic effect of metformin monotherapy with metformin and acupuncture combined therapy on weight loss and insulin sensitivity in diabetic patients. ( Firouzjaei, A; Li, GC; Liu, WX; Wang, N; Zhu, BM, 2016)
"Titrated canagliflozin significantly improved HbA1c, FPG, body weight and SBP, and was generally well tolerated over 26 weeks in patients with T2DM as add-on to metformin and sitagliptin."5.22Efficacy and safety of titrated canagliflozin in patients with type 2 diabetes mellitus inadequately controlled on metformin and sitagliptin. ( Aggarwal, N; Alba, M; Cao, A; Fung, A; Pfeifer, M; Rodbard, HW; Seufert, J, 2016)
"To provide evidence-based options on how to intensify basal insulin, we explored head-to-head prandial interventions in overweight patients with type 2 diabetes inadequately controlled on basal insulin glargine with or without 1-3 oral antidiabetic agents (OADs)."5.22Prandial Options to Advance Basal Insulin Glargine Therapy: Testing Lixisenatide Plus Basal Insulin Versus Insulin Glulisine Either as Basal-Plus or Basal-Bolus in Type 2 Diabetes: The GetGoal Duo-2 Trial. ( Aronson, R; Gentile, S; Guerci, B; Hanefeld, M; Heller, S; Perfetti, R; Rosenstock, J; Roy-Duval, C; Souhami, E; Tinahones, FJ; Wardecki, M; Ye, J, 2016)
"Subjects insufficiently controlled with sitagliptin who switch to liraglutide can obtain clinically relevant reductions in glycaemia and body weight, without compromising safety."5.22Efficacy and safety of switching from sitagliptin to liraglutide in subjects with type 2 diabetes (LIRA-SWITCH): a randomized, double-blind, double-dummy, active-controlled 26-week trial. ( Bailey, TS; Kaltoft, MS; Maislos, M; Rao, PV; Takács, R; Thomsen, AB; Tinahones, FJ; Tsoukas, GM, 2016)
"We previously reported that dapagliflozin versus placebo as add-on to saxagliptin plus metformin resulted in greater reductions in glycated haemoglobin (A1C), fasting plasma glucose (FPG) and body weight (BW) after 24 weeks of treatment in patients with type 2 diabetes (T2D)."5.22Efficacy and safety of triple therapy with dapagliflozin add-on to saxagliptin plus metformin over 52 weeks in patients with type 2 diabetes. ( Chen, H; Garcia-Sanchez, R; González González, JG; Hansen, L; Herrera Marmolejo, M; Iqbal, N; Johnsson, E; Mathieu, C, 2016)
"To evaluate the proportion of patients with type 2 diabetes mellitus (T2DM) achieving reductions in both glycated hemoglobin (HbA1c) and body weight with canagliflozin, a sodium glucose co-transporter 2 inhibitor, versus sitagliptin over 52 weeks."5.22Canagliflozin provides greater attainment of both HbA1c and body weight reduction versus sitagliptin in patients with type 2 diabetes. ( Canovatchel, W; Davidson, JA; Jodon, H; Lavalle-González, FJ; Qiu, R; Schernthaner, G; Vijapurkar, U, 2016)
"Triple therapy with saxagliptin add-on to dapagliflozin plus metformin for 52 weeks resulted in sustained improvements in glycaemic control without an increase in body weight or increased risk of hypoglycaemia."5.22One-year efficacy and safety of saxagliptin add-on in patients receiving dapagliflozin and metformin. ( Aggarwal, N; Chen, H; Chin, A; Garcia-Hernandez, P; Hansen, L; Iqbal, N; Johnsson, E; Matthaei, S, 2016)
"The study will evaluate whether metformin can result in favorable changes in breast density, select proteins and hormones, products of body metabolism, and body weight and composition."5.22Phase II study of metformin for reduction of obesity-associated breast cancer risk: a randomized controlled trial protocol. ( Altbach, M; Chalasani, P; Chow, HH; Galons, JP; Martinez, JA; Roe, D; Stopeck, A; Thompson, PA; Thomson, CA; Villa-Guillen, DE, 2016)
"Metformin has been used for alleviating metabolic abnormalities in patients with schizophrenia."5.22Effects of Low Dose Metformin on Metabolic Traits in Clozapine-Treated Schizophrenia Patients: An Exploratory Twelve-Week Randomized, Double-Blind, Placebo-Controlled Study. ( Chen, CH; Chen, PY; Chiu, CC; Huang, MC; Lin, SK; Lin, YK; Lu, ML, 2016)
" Women were randomized to intensive lifestyle change (ILS) with the goals of weight reduction of at least 7% of initial weight and 150 min per week of moderate-intensity exercise, metformin 850 mg twice a day, or placebo administered twice a day."5.20Weight loss increases follicle stimulating hormone in overweight postmenopausal women [corrected]. ( Barrett-Connor, E; Golden, SH; Kim, C; Kong, S; Labrie, F; Nan, B; Randolph, JF, 2015)
"Canagliflozin improved glycaemic control, reduced body weight and systolic blood pressure, and was generally well tolerated in patients aged 55-80 years with T2DM over 104 weeks."5.20Long-term efficacy and safety of canagliflozin over 104 weeks in patients aged 55-80 years with type 2 diabetes. ( Bode, B; Fung, A; Harris, S; Meininger, G; Stenlöf, K; Sullivan, D; Usiskin, K, 2015)
"In patients completing 4 years of treatment, dapagliflozin was well tolerated and associated with sustained glycaemic efficacy and greater reductions in body weight and SBP versus glipizide."5.20Long-term glycaemic response and tolerability of dapagliflozin versus a sulphonylurea as add-on therapy to metformin in patients with type 2 diabetes: 4-year data. ( Del Prato, S; Durán-Garcia, S; Maffei, L; Nauck, M; Parikh, S; Rohwedder, K; Theuerkauf, A, 2015)
"Ertugliflozin (1-25 mg/day) improved glycaemic control, body weight and blood pressure in patients with T2DM suboptimally controlled on metformin, and was well tolerated."5.20Dose-ranging efficacy and safety study of ertugliflozin, a sodium-glucose co-transporter 2 inhibitor, in patients with type 2 diabetes on a background of metformin. ( Amin, NB; Jain, SM; Lee, DS; Nucci, G; Rusnak, JM; Wang, X, 2015)
"Adding liraglutide to a basal insulin analogue ± metformin significantly improved glycaemic control, body weight and systolic blood pressure compared with placebo."5.20Efficacy and safety of liraglutide versus placebo added to basal insulin analogues (with or without metformin) in patients with type 2 diabetes: a randomized, placebo-controlled trial. ( Ahmann, A; Boopalan, A; de Loredo, L; Lahtela, JT; Nauck, MA; Rodbard, HW; Rosenstock, J; Tornøe, K, 2015)
" This study was conducted as an exploratory analysis to clarify the effects of liraglutide, a GLP-1RA, on beta cell function, fat distribution and pancreas volume compared with metformin in Japanese overweight/obese patients with T2DM."5.20Effects of Liraglutide Monotherapy on Beta Cell Function and Pancreatic Enzymes Compared with Metformin in Japanese Overweight/Obese Patients with Type 2 Diabetes Mellitus: A Subpopulation Analysis of the KIND-LM Randomized Trial. ( Cobelli, C; Irie, J; Itoh, H; Jinzaki, M; Kawai, T; Manesso, E; Meguro, S; Saisho, Y; Sugiura, H; Tanaka, K; Tanaka, M, 2015)
"The effect of metformin on weight reduction in polycystic ovary syndrome (PCOS) is often unsatisfactory."5.19Short-term combined treatment with liraglutide and metformin leads to significant weight loss in obese women with polycystic ovary syndrome and previous poor response to metformin. ( Janez, A; Jensterle Sever, M; Kocjan, T; Kravos, NA; Pfeifer, M, 2014)
"Roflumilast added to metformin reduced body weight in obese women with PCOS, primarily due to a loss of fat mass."5.19Phosphodiesterase 4 inhibition as a potential new therapeutic target in obese women with polycystic ovary syndrome. ( Janez, A; Jensterle, M; Kocjan, T, 2014)
"To study the effect of metformin on metabolic parameters, body weight (BW), and waist circumference (WC) in patients with abdominal obesity (AO)."5.19[Efficacy of metformin in abdominal obesity]. ( Kichigin, VA; Markova, TN; Mkrtumian, AM; Podachina, SV; Zhuchkova, SM, 2014)
" Patients also underwent a combined euglycemic, hyperinsulinemic, and hyperglycemic clamp with subsequent arginine stimulation to assess insulin sensitivity and insulin secretion."5.17Variation in inflammatory markers and glycemic parameters after 12 months of exenatide plus metformin treatment compared with metformin alone: a randomized placebo-controlled trial. ( Carbone, A; Ciccarelli, L; Derosa, G; Fogari, E; Franzetti, IG; Maffioli, P; Piccinni, MN; Querci, F, 2013)
"Many studies have shown that metformin can decrease body weight and improve metabolic abnormalities in patients with schizophrenia."5.17Effects of adjunctive metformin on metabolic traits in nondiabetic clozapine-treated patients with schizophrenia and the effect of metformin discontinuation on body weight: a 24-week, randomized, double-blind, placebo-controlled study. ( Chen, CH; Chiu, CC; Huang, MC; Kao, CF; Kuo, PH; Lin, SK; Lu, ML, 2013)
"Canagliflozin improved glycaemia and reduced body weight vs placebo (week 26) and sitagliptin (week 52) and was generally well tolerated in patients with type 2 diabetes on metformin."5.17Efficacy and safety of canagliflozin compared with placebo and sitagliptin in patients with type 2 diabetes on background metformin monotherapy: a randomised trial. ( Canovatchel, W; Davidson, J; Januszewicz, A; Lavalle-González, FJ; Meininger, G; Qiu, R; Tong, C, 2013)
"The glucose-lowering efficiency of combination therapy with metformin + vildagliptin, a DPP-4 inhibitor, was comparable with that of a metformin + SU combination, but safer with respect to the risk of developing hypoglycemia."5.17[A combination of dipeptidyl peptidase-4 inhibitor and metformin in the treatment of patients with type 2 diabetes mellitus: effective control of glycemia, weight, and quantitative body composition]. ( Aleksandrov, AA; Chernova, TO; Dedov, II; Il'in, AV; Shestakova, MV; Shmushkovich, IA; Suhareva, OIu, 2013)
"Compared with metformin, exenatide is better to control blood glucose, reduces body weight and improves hepatic enzymes, attenuating NAFLD in patients with T2DM concomitant with NAFLD."5.17Exenatide improves type 2 diabetes concomitant with non-alcoholic fatty liver disease. ( Fan, H; Pan, Q; Xu, Y; Yang, X, 2013)
"These results show that in obese patients with type 2 diabetes, DPP-4 inhibitors treatment in combination with metformin was associated with improvements in glycaemic control, and a reduction in body weight."5.17The effects of dipeptidyl peptidase-4 inhibitors in treatment of obese patients with type 2 diabetes. ( Coric, J; Dizdarevic-Bostandzic, A; Djelilovic-Vranic, J; Izetbegovic, S; Karamehic, J; Macic-Dzankovic, A; Panjeta, M; Velija-Asimi, Z, 2013)
"In patients with type 2 diabetes, empagliflozin resulted in dose-dependent, clinically meaningful reductions in HbA1c and FPG, and reductions in body weight compared with placebo."5.17A Phase IIb, randomized, placebo-controlled study of the SGLT2 inhibitor empagliflozin in patients with type 2 diabetes. ( Ferrannini, E; Hantel, S; Pinnetti, S; Seewaldt-Becker, E; Seman, L; Woerle, HJ, 2013)
"We tested genetic associations with weight loss and weight regain in the Diabetes Prevention Program, a randomized controlled trial of weight loss-inducing interventions (lifestyle and metformin) versus placebo."5.16Genetic predictors of weight loss and weight regain after intensive lifestyle modification, metformin treatment, or standard care in the Diabetes Prevention Program. ( Delahanty, LM; Florez, JC; Franks, PW; Jablonski, KA; Kahn, SE; Knowler, WC; McCaffery, JM; Pan, Q; Shuldiner, A; Watson, KE, 2012)
" The body weight, body mass index, fasting insulin and insulin resistance index decreased significantly in the metformin group, but increased in the placebo group during the 12-week follow-up period."5.16Metformin for treatment of antipsychotic-induced weight gain: a randomized, placebo-controlled study. ( Liang, GM; Tong, JH; Wang, M; Wang, XZ; Yan, HF; Zhu, G, 2012)
"Eighty-four women (ages 18-40 years) with first-episode schizophrenia who suffered from amenorrhea during antipsychotic treatment were randomly assigned, in a double-blind study design, to receive 1000 mg/day of metformin or placebo in addition to their antipsychotic treatment for 6 months."5.16Metformin for treatment of antipsychotic-induced amenorrhea and weight gain in women with first-episode schizophrenia: a double-blind, randomized, placebo-controlled study. ( Chan, PK; Davis, JM; Gao, K; Guo, XF; Jin, H; Ou, JJ; Shao, P; Twamley, EW; Wang, J; Wu, RR; Zhao, JP, 2012)
" This study aimed to determine the effect of metformin on body weight, body composition, metabolic risk factors and reproductive hormone levels in overweight or obese young women compared to placebo and comprehensive lifestyle intervention."5.15The effect of comprehensive lifestyle intervention or metformin on obesity in young women. ( Clifton, PM; Lim, SS; Noakes, M; Norman, RJ, 2011)
"Metformin had modest but favorable effects on body weight, body composition, and glucose homeostasis in obese insulin-resistant children participating in a low-intensity weight-reduction program."5.15Effects of metformin on body weight and body composition in obese insulin-resistant children: a randomized clinical trial. ( Brady, SM; Calis, KA; Kozlosky, M; Krakoff, J; McDuffie, JR; Reynolds, JC; Salaita, CG; Sebring, NG; Yanovski, JA, 2011)
"Comparing the effects of metformin or orlistat on hormone, lipid profile and ovulation status in obese women with polycystic ovary syndrome."5.15The effects of metformin or orlistat on obese women with polycystic ovary syndrome: a prospective randomized open-label study. ( Aflatoonian, A; Ghandi, S; Moghaddam, MH; Tabibnejad, N, 2011)
"The aim of this study was to evaluate the effect of exenatide compared to glimepiride on body weight, glycemic control and insulin resistance in type 2 diabetic patients taking metformin."5.15Exenatide or glimepiride added to metformin on metabolic control and on insulin resistance in type 2 diabetic patients. ( Bonaventura, A; Bossi, AC; Derosa, G; Fogari, E; Franzetti, IG; Guazzini, B; Maffioli, P; Putignano, P; Querci, F; Testori, G, 2011)
" Pioglitazone treatment (n = 10) reduced hepatic fat as assessed by magnetic resonance spectroscopy, despite a significant increase in body weight (Δ = 3."5.15Exenatide decreases hepatic fibroblast growth factor 21 resistance in non-alcoholic fatty liver disease in a mouse model of obesity and in a randomised controlled trial. ( Bajaj, M; Chan, L; Gonzalez, EV; Gutierrez, A; Jogi, M; Krishnamurthy, R; Muthupillai, R; Samson, SL; Sathyanarayana, P, 2011)
"The presence of fatty liver per ultrasound and liver-associated enzymes were measured in a select cohort of youth with both obesity and insulin resistance, and the effect of metformin on these parameters evaluated."5.14Treatment of non-alcoholic fatty liver disease with metformin versus lifestyle intervention in insulin-resistant adolescents. ( Ehlers, LB; Love-Osborne, K; Nadeau, KJ; Zeitler, PS, 2009)
"Addition of rosiglitazone to glucose-lowering therapy in people with type 2 diabetes is confirmed to increase the risk of heart failure and of some fractures, mainly in women."5.14Rosiglitazone evaluated for cardiovascular outcomes in oral agent combination therapy for type 2 diabetes (RECORD): a multicentre, randomised, open-label trial. ( Beck-Nielsen, H; Curtis, PS; Gomis, R; Hanefeld, M; Home, PD; Jones, NP; Komajda, M; McMurray, JJ; Pocock, SJ, 2009)
" Vildagliptin provided additional HbA(1c) lowering to that achieved with metformin alone and comparable to that achieved with pioglitazone, with only pioglitazone causing weight gain."5.14Comparison of vildagliptin and pioglitazone in patients with type 2 diabetes inadequately controlled with metformin. ( Bolli, G; Colin, L; Dotta, F; Goodman, M; Minic, B, 2009)
"Clozapine is the most effective agent in treatment-resistant schizophrenia."5.14Extended release metformin for metabolic control assistance during prolonged clozapine administration: a 14 week, double-blind, parallel group, placebo-controlled study. ( Baptista, T; Carrizo, E; Connell, L; de Baptista, EA; Fernández, I; Fernández, V; Mogollón, J; Prieto, D; Sandia, I; Valbuena, D, 2009)
"The aim of the study was to compare the effects of the addition of sitagliptin or metformin to pioglitazone monotherapy in poorly controlled type 2 diabetes mellitus patients on body weight, glycemic control, beta-cell function, insulin resistance, and inflammatory state parameters."5.14Effects of sitagliptin or metformin added to pioglitazone monotherapy in poorly controlled type 2 diabetes mellitus patients. ( Ciccarelli, L; Cicero, AF; D'Angelo, A; Derosa, G; Ferrari, I; Franzetti, IG; Gadaleta, G; Maffioli, P; Piccinni, MN; Querci, F; Ragonesi, PD; Salvadeo, SA, 2010)
"The aim of this study was to investigate the effects of pioglitazone or metformin on bone mass and atherosclerosis in patients with type 2 diabetes."5.14Baseline atherosclerosis parameter could assess the risk of bone loss during pioglitazone treatment in type 2 diabetes mellitus. ( Kanazawa, I; Kurioka, S; Sugimoto, T; Yamaguchi, T; Yamamoto, M; Yamauchi, M; Yano, S, 2010)
" The aim of our study was to evaluate the effects of exenatide compared to glibenclamide on body weight, glycemic control, beta-cell function, insulin resistance, and inflammatory state in patients with diabetes."5.14Exenatide versus glibenclamide in patients with diabetes. ( Ciccarelli, L; Cicero, AF; D'Angelo, A; Derosa, G; Ferrari, I; Franzetti, IG; Gadaleta, G; Maffioli, P; Piccinni, MN; Querci, F; Ragonesi, PD; Salvadeo, SA, 2010)
"Pioglitazone was associated with a rapid increase in body weight and an increase in diurnal proximal sodium reabsorption, without any change in renal haemodynamics or in the modulation of the renin-angiotensin aldosterone system to changes in salt intake."5.14Effects of the peroxisome proliferator-activated receptor (PPAR)-gamma agonist pioglitazone on renal and hormonal responses to salt in diabetic and hypertensive individuals. ( Burnier, M; Deleaval, P; Jornayvaz, FR; Maillard, M; Nussberger, J; Pechere-Bertschi, A; Vinciguerra, M; Zanchi, A, 2010)
"Obese European adolescents' insulin sensitivity improved without weight change during placebo or metformin intervention in addition to lifestyle intervention."5.14Metformin and placebo therapy both improve weight management and fasting insulin in obese insulin-resistant adolescents: a prospective, placebo-controlled, randomized study. ( Bürmann, M; Grüters, A; Holl, RW; Hübel, H; Krude, H; l'Allemand, D; Martus, P; Wiegand, S, 2010)
"Vildagliptin add-on has similar efficacy to glimepiride after 2 years' treatment, with markedly reduced hypoglycaemia risk and no weight gain."5.14Vildagliptin add-on to metformin produces similar efficacy and reduced hypoglycaemic risk compared with glimepiride, with no weight gain: results from a 2-year study. ( Ahren, B; Couturier, A; Dejager, S; Ferrannini, E; Foley, JE; Fonseca, V; Matthews, DR; Zinman, B, 2010)
"To determine whether metformin treatment for 6 months is effective in reducing body weight and hyperinsulinemia and also ameliorating insulin sensitivity indices in obese adolescents with hyperinsulinemia."5.13Use of metformin in obese adolescents with hyperinsulinemia: a 6-month, randomized, double-blind, placebo-controlled clinical trial. ( Atabek, ME; Pirgon, O, 2008)
"Metformin was reported to improve the alterations of endothelial reactivity in normal-weight subjects with polycystic ovary syndrome (PCOS)."5.13Metformin improves endothelial function in normoinsulinemic PCOS patients: a new prospective. ( Bompiani, A; Costantini, B; Cristello, F; Giuliani, M; Guido, M; Lanzone, A; Macrì, F; Romualdi, D; Selvaggi, L, 2008)
"One hundred forty-two nondiabetic women with polycystic ovary syndrome (PCOS) who had at least one live-birth (LB) pregnancy on metformin diet (172 pregnancies, 180 LBs)."5.13Prevention of gestational diabetes by metformin plus diet in patients with polycystic ovary syndrome. ( Aregawi, D; Glueck, CJ; Pranikoff, J; Wang, P, 2008)
"The second generation antipsychotic drugs, such as risperidone, olanzapine, and quetiapine, are effective in treating patients with schizophrenia and have been considered as the first line therapy."5.13Metformin for metabolic dysregulation in schizophrenic patients treated with olanzapine. ( Chen, CH; Chiu, CC; Huang, MC; Liu, HC; Lu, ML; Wu, TH, 2008)
"Effects of metformin and pioglitazone on body weight are clearly different."5.13Metformin, but not pioglitazone, decreases postchallenge plasma ghrelin levels in type 2 diabetic patients: a possible role in weight stability? ( Horie, H; Ishibashi, S; Kusaka, I; Nagasaka, S, 2008)
"To investigate the effects of extended-release metformin (MXR) compared with immediate-release metformin (MIR) on post-prandial glycaemic excursion, chronic glycaemia, lipid profiles, insulin resistance and islet function in type 2 diabetes."5.13The metabolic effects of once daily extended-release metformin in patients with type 2 diabetes: a multicentre study. ( Gao, H; Hong, T; Wang, C; Xiao, W; Yang, J; Yang, W; Yang, Y; Zhang, J, 2008)
"We evaluated exenatide (EX) and metformin (MET), alone and in combination (COM), on menstrual cyclicity, hormonal parameters, metabolic profiles, and inflammatory markers in overweight, insulin-resistant women with PCOS."5.13Comparison of single and combined treatment with exenatide and metformin on menstrual cyclicity in overweight women with polycystic ovary syndrome. ( Bhushan, M; Bhushan, R; Elkind-Hirsch, K; Marrioneaux, O; Vernor, D, 2008)
"The present study aimed to investigate the effects of metformin on body weight in polycystic ovary syndrome (PCOS) patients by model-based meta-analysis (MBMA)."5.12Effects of metformin on body weight in polycystic ovary syndrome patients: model-based meta-analysis. ( Chen, X; He, S; Wang, D, 2021)
"This study was designed to assess the usefulness of a model-based index of insulin sensitivity during an oral glucose tolerance test (OGTT) in the identification of possible changes in this metabolic parameter produced by pharmacological agents known to be potent insulin sensitizers, that is metformin (M) and thiazolidinedione (T)."5.12Insulin sensitivity during oral glucose tolerance test and its relations to parameters of glucose metabolism and endothelial function in type 2 diabetic subjects under metformin and thiazolidinedione. ( Hanusch-Enserer, U; Kautzky-Willer, A; Ludvik, B; Pacini, G; Prager, R; Tura, A; Wagner, OF; Winzer, C, 2006)
"The authors hypothesized that a metformin (MET)-diet would improve symptoms of idiopathic intracranial hypertension (IIH) in women who also had polycystic ovary syndrome (PCOS) or hyperinsulinemia without PCOS."5.12Changes in weight, papilledema, headache, visual field, and life status in response to diet and metformin in women with idiopathic intracranial hypertension with and without concurrent polycystic ovary syndrome or hyperinsulinemia. ( Aregawi, D; Glueck, CJ; Goldenberg, N; Golnik, KC; Sieve, L; Wang, P, 2006)
" However, body weight, waist circumference, fasting serum levels of insulin and C-peptide were lower and less number of patients experienced hypoglycaemia during treatment with metformin vs."5.12Targeting hyperglycaemia with either metformin or repaglinide in non-obese patients with type 2 diabetes: results from a randomized crossover trial. ( Frandsen, M; Lund, SS; Parving, HH; Pedersen, O; Schalkwijk, CG; Smidt, UM; Stehouwer, CD; Tarnow, L; Vaag, A, 2007)
"Metformin may safely assist olanzapine-treated patients in body weight and carbohydrate metabolism control."5.12Metformin as an adjunctive treatment to control body weight and metabolic dysfunction during olanzapine administration: a multicentric, double-blind, placebo-controlled trial. ( Baptista, T; Beaulieu, S; Carrizo, E; Connell, L; Dávila, A; de Baptista, EA; El Fakih, Y; Fernández, V; Galeazzi, T; Gutiérrez, MA; Rangel, N; Serrano, A; Servigna, M; Uzcátegui, E; Uzcátegui, M, 2007)
"The objective of the study was to evaluate the effects of metformin suspension on insulin sensitivity in PCOS patients."5.12Insulin sensitivity after metformin suspension in normal-weight women with polycystic ovary syndrome. ( De Feo, P; Falbo, A; Manguso, F; Orio, F; Palomba, S; Russo, T; Tolino, A; Zullo, F, 2007)
"65 kg/m(2)) hirsute women with polycystic ovary syndrome and normal insulin sensitivity were treated with 850 mg metformin orally, three times daily, for 4 months."5.12Metformin in normal-weight hirsute women with polycystic ovary syndrome with normal insulin sensitivity. ( Baracat, EC; Halpern, A; Maciel, GA; Marcondes, JA; Yamashita, SA, 2007)
"Our aim was to assess the effects of metformin on menstrual frequency, fasting plasma glucose (FPG), insulin resistance assessed as HOMA-index, weight, waist/hip ratio, blood pressure (BP), serum lipids, and testosterone levels in women with polycystic ovary syndrome (PCOS) METHODS: In a randomized, controlled, double-blinded setup, 56 women aged 18-45 with PCOS were treated with either metformin 850 mg or placebo twice daily for 6 months."5.12Efficacy of metformin in obese and non-obese women with polycystic ovary syndrome: a randomized, double-blinded, placebo-controlled cross-over trial. ( Flyvbjerg, A; Kesmodel, U; Lauszus, FF; Trolle, B, 2007)
" Objective To prospectively evaluate if administration of metformin to obese, diabetic patients with primary hypothyroidism on stable thyroxine replacement doses modifies TSH levels."5.12Metformin reduces thyrotropin levels in obese, diabetic women with primary hypothyroidism on thyroxine replacement therapy. ( Cordido, F; Isidro, ML; Nemiña, R; Penín, MA, 2007)
"To determine the clinical, hormonal, and biochemical effects of metformin therapy in obese and nonobese patients with polycystic ovary syndrome (PCOS)."5.11Nonobese women with polycystic ovary syndrome respond better than obese women to treatment with metformin. ( Abi Haidar, M; Alves da Motta, EL; Baracat, EC; de Lima, GR; Maciel, GA; Soares Júnior, JM, 2004)
"In a prospective observational study of 42 pregnancies in 39 Caucasian women (age 30 +/- 4 years) with polycystic ovary syndrome (PCOS), we examined effects of metformin on maternal insulin, insulin resistance (IR), insulin secretion (IS), weight gain, development of gestational diabetes (GD), testosterone and plasminogen activator inhibitor activity."5.11Metformin during pregnancy reduces insulin, insulin resistance, insulin secretion, weight, testosterone and development of gestational diabetes: prospective longitudinal assessment of women with polycystic ovary syndrome from preconception throughout preg ( Glueck, CJ; Goldenberg, N; Loftspring, M; Sherman, A; Wang, P, 2004)
"We prospectively assessed growth and motor-social development during the first 18 months of life in 126 live births (122 pregnancies) to 109 women with polycystic ovary syndrome (PCOS) who conceived on and continued metformin (1."5.11Height, weight, and motor-social development during the first 18 months of life in 126 infants born to 109 mothers with polycystic ovary syndrome who conceived on and continued metformin through pregnancy. ( Glueck, CJ; Goldenberg, N; Loftspring, M; Pranikoff, J; Sieve, L; Wang, P, 2004)
"Metformin improves insulin sensitivity, which is correlated to phospholipid fatty acid composition in obese type 2 diabetics."5.11Effect of metformin vs. placebo treatment on serum fatty acids in non-diabetic obese insulin resistant individuals. ( Christophe, AB; Feyen, E; Giri, M; Rodríguez, Y, 2004)
" metformin on the hormonal and biochemical features of patients with polycystic ovarian syndrome (PCOS)."5.11Orlistat is as beneficial as metformin in the treatment of polycystic ovarian syndrome. ( Atkin, SL; Holding, S; Jayagopal, V; Jennings, PE; Kilpatrick, ES, 2005)
" Although long-term treatment with metformin can increase Hcy levels in patients with type II diabetes mellitus or coronary heart disease, it is becoming an increasingly accepted and widespread medication in polycystic ovary syndrome (PCOS)."5.11Homocysteine levels in women with polycystic ovary syndrome treated with metformin versus rosiglitazone: a randomized study. ( Aslan, E; Bagis, T; Erkanli, S; Haydardedeoglu, B; Kilicdag, EB; Tarim, E; Zeyneloglu, HB, 2005)
"The aim of the current study was to assess the effects of B-group vitamins and folic acid administration on serum levels of homocysteine (Hcy) in patients with polycystic ovarian syndrome (PCOS) on short-term metformin treatment."5.11Administration of B-group vitamins reduces circulating homocysteine in polycystic ovarian syndrome patients treated with metformin: a randomized trial. ( Aslan, E; Bagis, T; Erkanli, S; Haydardedeoglu, B; Kilicdag, EB; Kuscu, E; Simsek, E; Tarim, E, 2005)
" The aim of this study was to assess the effects of rosiglitazone and metformin on cardiovascular disease risk factors such as insulin resistance, oxidative stress and homocysteine levels in lean patients with polycystic ovary syndrome (PCOS)."5.11The effects of rosiglitazone and metformin on oxidative stress and homocysteine levels in lean patients with polycystic ovary syndrome. ( Arslan, M; Ayvaz, G; Bukan, N; Cakir, N; Karakoç, A; Törüner, F; Yilmaz, M, 2005)
" There was a significant improvement in hirsutism at the end of the metformin phase compared with placebo: F-G score 15."5.10The effect of metformin on hirsutism in polycystic ovary syndrome. ( Gordon, D; Kelly, CJ, 2002)
" Changes in A1C, fasting plasma glucose, fructosamine, serum lipids, body weight, and 2-h postprandial glucose after a standardized meal were assessed after 16 wk of treatment."5.10Efficacy of glyburide/metformin tablets compared with initial monotherapy in type 2 diabetes. ( Bruce, S; Dandona, P; Donovan, DS; Garber, AJ; Park, JS, 2003)
"The results of this study confirm that sibutramine, orlistat and metformin are all effective and safe medications that reduce cardiovascular risk and can decrease the risk of type 2 diabetes mellitus in obese females."5.10Evaluation of the safety and efficacy of sibutramine, orlistat and metformin in the treatment of obesity. ( BascilTutuncu, N; Gokcel, A; Gumurdulu, Y; Guvener, N; Karakose, H; Melek Ertorer, E; Tanaci, N, 2002)
"The purpose of this study was to assess the effect of orlistat, a gastrointestinal lipase inhibitor, on body weight, glycemic control, and cardiovascular risk factors in metformin-treated type 2 diabetic patients."5.10Effect of orlistat in overweight and obese patients with type 2 diabetes treated with metformin. ( Anderson, JW; Aronne, L; Doyle, M; Foreyt, J; Hollander, P; Klein, S; Leiter, L; Miles, JM; Wadden, T, 2002)
" Body weight, fasting plasma glucose, HbA(1c), blood lactate, total cholesterol and HDL-cholesterol, and triglycerides were measured at the beginning and end of T1 and T5, and end of T2, T3, T6 and T7; postprandial plasma glucose, fasting and postprandial plasma insulin and C-peptide were evaluated at the beginning of T1 and T5, and end of T3 and T7."5.09A comparison of preconstituted, fixed combinations of low-dose glyburide plus metformin versus high-dose glyburide alone in the treatment of type 2 diabetic patients. ( Coppini, A; Erle, G; Lora, L; Lovise, S; Marchetti, P; Merante, D; Stocchiero, C, 1999)
"To assess the effect of metformin on insulin sensitivity, glucose tolerance and components of the metabolic syndrome in patients with impaired glucose tolerance (IGT)."5.09Metabolic effects of metformin in patients with impaired glucose tolerance. ( Eriksson, JG; Forsén, B; Groop, L; Gullström, M; Häggblom, M; Lehtovirta, M; Taskinen, MR, 2001)
"Metformin lowered the LDL/HDL-cholesterol ratio by 12 and 6% at weeks 4 and 12, respectively, and reduced body weight by 1."5.08Metformin improves blood lipid pattern in nondiabetic patients with coronary heart disease. ( Bjerve, KS; Carlsen, SM; Følling, I; Rossvoll, O, 1996)
" Liraglutide is a glucagon-like peptide-1 receptor agonist that promotes sustained weight loss, as well as abdominal fat reduction, in individuals with obesity, prediabetes, and type 2 diabetes mellitus."5.05Liraglutide: New Perspectives for the Treatment of Polycystic Ovary Syndrome. ( Constantinidou, KG; Filippou, PK; Papaetis, GS; Stylianou, CS, 2020)
"The present study firstly provided quantitative information for metformin effects on weight in different disease states, including patients with type 2 diabetes mellitus, patients with antipsychotic induced weight gain, patients with obesity."5.05Time course and dose effect of metformin on weight in patients with different disease states. ( Chen, X; Li, ZP; Wang, DD, 2020)
"08]), but less hypoglycemia as add-on to metformin (odds ratio [OR] 0."5.01Sodium-Glucose Co-Transporter 2 Inhibitors Compared with Sulfonylureas in Patients with Type 2 Diabetes Inadequately Controlled on Metformin: A Meta-Analysis of Randomized Controlled Trials. ( Chen, Z; Li, G, 2019)
"In September 2018, we searched PubMed, Embase, and the Cochrane Library for studies published in English using the keywords metformin, obesity/overweight, and weight loss."4.98Efficacy of Metformin Treatment with Respect to Weight Reduction in Children and Adults with Obesity: A Systematic Review. ( Knibbe, CAJ; Lentferink, YE; van der Vorst, MMJ, 2018)
"English-language trials of benefits or harms of screening or treatment (behavior-based, orlistat, metformin) for overweight or obesity in children aged 2 through 18 years, conducted in or recruited from health care settings."4.95Screening for Obesity and Intervention for Weight Management in Children and Adolescents: Evidence Report and Systematic Review for the US Preventive Services Task Force. ( Burda, BU; Eder, M; Evans, CV; Lozano, P; O'Connor, EA; Walsh, ES, 2017)
"We conducted a systematic-review and meta-analysis of metformin versus placebo for change in weight and metabolic syndrome for people on clozapine without diabetes mellitus."4.93Metformin for Clozapine Associated Obesity: A Systematic Review and Meta-Analysis. ( Kisely, S; Leung, J; Russell, AW; Siskind, DJ; Wysoczanski, D, 2016)
"Adding different AHAs to metformin was associated with varying effects on HbA1c, BW, SBP, hypoglycemia, UTI and GTI which should impact clinician choice when selecting adjunctive therapy."4.91Comparative efficacy and safety of antidiabetic drug regimens added to metformin monotherapy in patients with type 2 diabetes: a network meta-analysis. ( Coleman, CI; Doleh, Y; Kohn, CG; Mearns, ES; Saulsberry, WJ; Sobieraj, DM; White, CM; Zaccaro, E, 2015)
"SGLT-2 inhibition in combination with metformin is a potential therapeutic option based on its effects on glycemic control, body weight, and blood pressure, but further trials are required to refine this evidence."4.90Combinational therapy with metformin and sodium-glucose cotransporter inhibitors in management of type 2 diabetes: systematic review and meta-analyses. ( Dou, J; Lu, J; Zhang, Q, 2014)
" These options are mostly new and have the advantage a neutral or favourable (for GLP-1) effect on body weight in obese type 2 DM patient and the absence of any hypoglycaemic risk in both classes of incretins."4.89[Management of type 2 diabetes: new or previous agents, how to choose?]. ( Halimi, S, 2013)
"Sitagliptin is similar to metformin in reducing HbA1c, decreasing body weight, and improving the function of beta cells, but is inferior to metformin in improving insulin sensitivity."4.89Comparative effects of sitagliptin and metformin in patients with type 2 diabetes mellitus: a meta-analysis. ( Du, Q; Liang, YY; Wang, YJ; Wu, B; Yang, S; Zhao, YY, 2013)
" The traditional approach involves: i) metformin, acting mainly on fasting blood glucose; ii) sulphonylureas, that have shown a number of drawbacks, including the high risk of hypoglycemia; iii) pioglitazone, with a substantial effect on fasting and postprandial glucose and a low risk of hypoglycaemia; iv) insulin, that can be utilized with the basal or prandial approach."4.89What are the preferred strategies for control of glycaemic variability in patients with type 2 diabetes mellitus? ( Marangoni, A; Zenari, L, 2013)
" We conclude that metformin may prove useful in macrovascular disease reduction, while pramlintide, glucagon-like peptide-1 agonists, dipeptidyl peptidase-4 inhibitors and leptin co-therapies may reduce HbA(1c) , glucose variability, postprandial glucose excursions and body weight."4.89Potential role of non-insulin adjunct therapy in Type 1 diabetes. ( George, P; McCrimmon, RJ, 2013)
"In patients with type 2 diabetes who do not achieve the glycaemic targets with metformin alone, DPP-4 inhibitors can lower HbA(1c), in a similar way to sulfonylureas or pioglitazone, with neutral effects on body weight."4.88Dipeptidyl peptidase-4 inhibitors for treatment of type 2 diabetes mellitus in the clinical setting: systematic review and meta-analysis. ( Karagiannis, T; Matthews, DR; Paletas, K; Paschos, P; Tsapas, A, 2012)
"Metformin, an oral anti-diabetic drug, is being considered increasingly for treatment and prevention of cancer, obesity as well as for the extension of healthy lifespan."4.88Metformin in obesity, cancer and aging: addressing controversies. ( Berstein, LM, 2012)
"Substantial evidence confirms the weight benefits of metformin and shows that, of the newer available agents, glucagon-like peptide-1 (GLP-1) agonists and amylin analogs promote weight loss."4.87Weight beneficial treatments for type 2 diabetes. ( Caputo, S; Damçi, T; Khunti, K; Liebl, A; Meneghini, LF; Orozco-Beltran, D; Ross, SA, 2011)
" While metformin has been shown to attenuate weight gain and insulin resistance, not all studies have shown a benefit in the reduction of antipsychotic-induced weight gain and insulin resistance."4.86The effect of metformin on anthropometrics and insulin resistance in patients receiving atypical antipsychotic agents: a meta-analysis. ( Coleman, CI; Ehret, M; Goethe, J; Lanosa, M, 2010)
" Metformin has attracted attention as a potential treatment option because it is thought to result in weight reduction and improved glycemic control in obese patients with and without type 2 diabetes mellitus."4.86The adjunctive use of metformin to treat or prevent atypical antipsychotic-induced weight gain: a review. ( Ali, F; Dahmen, MM; Girrens, K; Khan, AY; Macaluso, M; McHale, RJ, 2010)
" Metformin has been evaluated in clinical studies to prevent or reduce weight gain and changes in metabolic parameters in non-diabetic subjects."4.85Changes in weight and metabolic parameters during treatment with antipsychotics and metformin: do the data inform as to potential guideline development? A systematic review of clinical studies. ( Bradley, AJ; Bushe, CJ; Doshi, S; Karagianis, J, 2009)
"To evaluate the efficacy and safety of metformin for weight management in overweight and obese patients without type 2 diabetes."4.84Role of metformin for weight management in patients without type 2 diabetes. ( Desilets, AR; Dhakal-Karki, S; Dunican, KC, 2008)
"The antidiabetic compound pioglitazone, an activator of the intracellular peroxisome proliferator-activated receptor-gamma, and decreases metabolic and vascular insulin resistance."4.83Pioglitazone: an antidiabetic drug with cardiovascular therapeutic effects. ( Forst, T; Pfützner, A; Schneider, CA, 2006)
"To assess the effectiveness of metformin in improving clinical and biochemical features of polycystic ovary syndrome."4.82Metformin in polycystic ovary syndrome: systematic review and meta-analysis. ( Flight, IH; Lord, JM; Norman, RJ, 2003)
"Metformin has become an established treatment for women with polycystic ovary syndrome, although controversy remains as to how effective it is and in which populations it should be used."4.82Metformin in polycystic ovary syndrome. ( Lord, J; Wilkin, T, 2004)
"The results differ concerning randomized controlled trials of the effects of metformin on blood glucose regulation and body weight."4.80Efficacy of metformin in the treatment of NIDDM. Meta-analysis. ( Johansen, K, 1999)
"Metformin, the most widely prescribed medication for obesity-associated type 2 diabetes (T2D), lowers plasma glucose levels, food intake, and body weight in rodents and humans, but the mechanistic site(s) of action remain elusive."4.31Metformin triggers a kidney GDF15-dependent area postrema axis to regulate food intake and body weight. ( Barros, DR; Bruce, K; Cherney, DZ; Chiu, JFM; Danaei, Z; Kuah, R; Lam, TKT; Li, RJW; Lim, YM; Mariani, LH; Reich, HN; Zhang, SY, 2023)
"We compared the efficacy and safety of beinaglutide, a glucagon-like peptide-1 (GLP-1) analogue with metformin in lowering the bodyweight of patients who were overweight/obese and non-diabetic."4.12Comparison of Beinaglutide Versus Metformin for Weight Loss in Overweight and Obese Non-diabetic Patients. ( Bi, Y; Feng, W; Fu, Y; Gao, L; Huang, H; Zhang, L; Zhang, N; Zhu, D, 2022)
"T2DM patients that performed regular exercise, had normal renal function and were receiving metformin were more likely to have clinically meaningful body weight reduction after one year treatment with dapagliflozin."4.12Predictors for successful weight reduction during treatment with Dapagliflozin among patients with type 2 diabetes mellitus in primary care. ( Huh, Y; Kim, YS, 2022)
"Fifty NMRI mice (7-8 weeks old) were randomly divided into five groups, including non-PCOS, PCOS and PCOS groups treated with clomiphene citrate (18 mg/kg body weight for 2 days), metformin (50 mg/100 g body weight for 30 days) and flutamide (10 mg/kg body weight injection for 15 days)."4.12Metformin, clomiphene citrate and flutamide effects on oocyte ultrastructure status and quality in PCOS mouse model. ( Esmaeilnezhad, S; Ghasemian, F, 2022)
"Linagliptin and its combination with metformin successfully ameliorated diabetic osteoporosis in HFD-fed mice possibly through modulation of BMP-2 and sclerostin."4.12Linagliptin in Combination With Metformin Ameliorates Diabetic Osteoporosis Through Modulating BMP-2 and Sclerostin in the High-Fat Diet Fed C57BL/6 Mice. ( Nirwan, N; Vohora, D, 2022)
" This study intends to examine the effects of sea buckthorn and metformin on body weight, water and feed intake, glycaemia, insulinemia, sorbitol accumulation and cataract development in Zucker diabetic fatty rats, which represent an animal model of type 2 Diabetes mellitus, as well as to characterize the individual content of bioactive substances and the antioxidant activity of sea buckthorn."4.12The consumption of sea buckthorn (Hippophae rhamnoides L.) effectively alleviates type 2 diabetes symptoms in spontaneous diabetic rats. ( Brindza, J; Capcarova, M; Dupak, R; Hrnkova, J; Ivanisova, E; Kalafova, A; Kovac, J; Prnova, MS; Schneidgenova, M; Simonova, N; Tokarova, K, 2022)
" After metformin and exenatide supplementation, body weight, chow intake and ovarian morphology were observed."4.02Metformin and exenatide upregulate hepatocyte nuclear factor-4α, sex hormone binding globulin levels and improve hepatic triglyceride deposition in polycystic ovary syndrome with insulin resistance rats. ( He, B; Li, X; Lv, B; Wang, D; Xing, C; Zhao, H, 2021)
"The present study evaluated the effects of dapagliflozin, a SGLT2 inhibitor, or dapagliflozin plus metformin versus metformin monotherapy in patients with metabolic syndrome."4.02Dapagliflozin, metformin, monotherapy or both in patients with metabolic syndrome. ( Cheng, L; Fan, Y; Fu, Q; Lin, W; Liu, F; Wu, X; Zhang, X; Zhou, L, 2021)
" Metformin is shown to lower body weight and adiposity, but the underlying mechanism is unclear."4.02Metformin effectively restores the HPA axis function in diet-induced obese rats. ( Balasubramanian, P; Herdt, TH; MohanKumar, PS; MohanKumar, SMJ; Shin, AC; Suryadevara, P; Zyskowski, J, 2021)
"Olanzapine treatment increased the body weight, blood glucose and triglyceride levels, and the number of adipocytes in the liver."4.02Coadministration of metformin prevents olanzapine-induced metabolic dysfunction and regulates the gut-liver axis in rats. ( Huang, HX; Liu, ZQ; Luo, C; Mao, XY; Wang, X; Zhou, HH, 2021)
" Metformin has potential effects on improving asthma airway inflammation."4.02Metformin alleviates allergic airway inflammation and increases Treg cells in obese asthma. ( Chen, M; Guo, Y; Hong, L; Jiang, S; Liu, S; Shi, J; Wang, Q; Yuan, X, 2021)
"To explore the effects of second-line combination therapies with metformin on body weight, HbA1c and health-related quality of life, as well as the risks of hypoglycaemia and further treatment intensification in the DISCOVER study, a 3-year, prospective, global observational study of patients with type 2 diabetes initiating second-line glucose-lowering therapy."4.02Associations between second-line glucose-lowering combination therapies with metformin and HbA1c, body weight, quality of life, hypoglycaemic events and glucose-lowering treatment intensification: The DISCOVER study. ( Charbonnel, B; Chen, H; Cooper, A; Gomes, MB; Ji, L; Khunti, K; Leigh, P; Nicolucci, A; Rathmann, W; Shestakova, MV; Siddiqui, A; Tang, F; Watada, H, 2021)
" Because previous data suggest the procognitive potential of the antidiabetic drug metformin, this study aimed to assess the effects of chronic clozapine and metformin oral administration (alone and in combination) on locomotor and exploratory activities and cognitive function in a reward-based test in control and a schizophrenia-like animal model (Wisket rats)."4.02Interaction of clozapine with metformin in a schizophrenia rat model. ( Adlan, LG; Benyhe, S; Büki, A; Heni, HE; Horvath, G; Kekesi, G; Kis, G; Szűcs, E, 2021)
" Berberine, which is a modulator of TRPV1, has proven antiobesity and antidiabetic potentials."3.96Berberine attenuated olanzapine-induced metabolic alterations in mice: Targeting transient receptor potential vanilloid type 1 and 3 channels. ( Bansal, Y; Bishnoi, M; Kondepudi, KK; Kuhad, A; Medhi, B; Singh, DP; Singh, R; Sodhi, RK, 2020)
"The current results suggest that exenatide is equivalent to metformin in controlling insulin resistance, body weight gain, improving liver function, suppressing inflammation, and attenuating NAFLD progression in male rats."3.96Exenatide ameliorates experimental non-alcoholic fatty liver in rats via suppression of toll-like receptor 4/NFκB signaling: Comparison to metformin. ( Ahmed, AAM; Khodeer, DM; Moustafa, YM; Saad, ZA; Zaitone, SA, 2020)
"What is the central question of this study? Studies reported the efficacy of metformin as a promising drug for preventing or treating of metabolic diseases."3.96Early metformin treatment improves pancreatic function and prevents metabolic dysfunction in early overfeeding male rats at adulthood. ( Alves, VS; de Moraes, AMP; de Oliveira, JC; Francisco, FA; Franco, CCDS; Malta, A; Martins, IP; Mathias, PCF; Matiusso, CCI; Miranda, RA; Moreira, VM; Pavanello, A; Prates, KV; Previate, C, 2020)
"Metformin has been reported to decrease insulin resistance and is associated with a lower risk of pregnancy-induced hypertension and preeclampsia."3.91Effect of Metformin on a Preeclampsia-Like Mouse Model Induced by High-Fat Diet. ( Cao, G; Cao, X; Li, L; Wang, F; Yi, W, 2019)
"This study evaluated the preventative effects of metformin (Met) on glucocorticoid (GC)-induced osteoporosis in a rat model, compared with alendronate (Aln)."3.91Preventative effects of metformin on glucocorticoid-induced osteoporosis in rats. ( Li, Q; Li, Y; Meng, Y; Shi, D; Zhang, H; Zhao, J; Zuo, L, 2019)
"In diet-induced obesity, metformin (MF) has weight-lowering effect and improves glucose homeostasis and insulin sensitivity."3.91The evidence of metabolic-improving effect of metformin in Ay/a mice with genetically-induced melanocortin obesity and the contribution of hypothalamic mechanisms to this effect. ( Bakhtyukov, A; Bayunova, L; Derkach, K; Romanova, I; Shpakov, A; Zakharova, I; Zorina, I, 2019)
"Metformin treatment did not affect food intake, body weight, and casual blood glucose levels within each mouse line during the 20-week feeding period."3.91Metformin Attenuates Early-Stage Atherosclerosis in Mildly Hyperglycemic Oikawa-Nagao Mice. ( Asai, A; Kawahara, M; Miyazawa, T; Nagao, M; Oikawa, S; Shuto, Y; Sugihara, H, 2019)
"Metformin decreased glucose concentrations, reduced metabolic syndrome, as well as insulin dose requirement more than insulin therapy alone, 1 year after treatment."3.88The effects of metformin in type 1 diabetes mellitus. ( Beysel, S; Cakal, E; Caliskan, M; Kizilgul, M; Ucan, B; Unsal, IO, 2018)
"Metformin or/and α-LA attenuated the severity of the DSS-induced colitis through improving the reductions in body weights, the DAI, the colonic oxidative stress markers, TNF-α, and NF-κB levels, and the morphological mucosal damage scores."3.88New insights on the modulatory roles of metformin or alpha-lipoic acid versus their combination in dextran sulfate sodium-induced chronic colitis in rats. ( Elaidy, SM; Essawy, SS; Hassan, MS; Samman, FS, 2018)
"These data suggest that metformin protects against bleomycin-induced pulmonary fibrosis through activation of AMPK and amelioration of TGF-β signaling pathways."3.88Metformin alleviates bleomycin-induced pulmonary fibrosis in rats: Pharmacological effects and molecular mechanisms. ( Arava, S; Arya, DS; Bhatia, J; Gamad, N; Malik, S; Suchal, K; Tomar, A; Vasisht, S, 2018)
"The biguanide metformin (MET) has been used during pregnancy for treatment of polycystic ovary syndrome and gestational diabetes."3.88Intrauterine exposure to metformin: Evaluation of endothelial and perivascular adipose tissue function in abdominal aorta of adult offspring. ( Akamine, EH; Ceravolo, GS; da Silva, MDV; de Andrade, FG; Gerardin, DCC; Montagnini, BG; Moura, KF; Novi, DRBS; Picinin, R; Silva, RNOD; Vidigal, CB, 2018)
" Ursolic acid, metformin, gliclazide and their combinations when administered daily for 30 days significantly improved insulin sensitivity apart from behavioral and biochemical alterations in stressed mice."3.88Synergistic action of ursolic acid and metformin in experimental model of insulin resistance and related behavioral alterations. ( Ahuja, S; Akhtar, A; Kumar, A; Mourya, A; Sah, SP, 2018)
"To evaluate the effect of metformin and pioglitazone on leutinizing hormone and follicle stimulating hormone receptor mRNA expression, hyperandrogenism and insulin resistance in high fat diet induced and letrozole induced PCOS in rats."3.88Insulin Sensitizers Modulate GnRH Receptor Expression in PCOS Rats. ( Patel, R; Shah, G, 2018)
"The present study aimed to investigate the effect of metformin on the induction of autophagy in the liver and adipose tissues of a mouse model of obesity."3.85Metformin ameliorates hepatic steatosis and improves the induction of autophagy in HFD‑induced obese mice. ( Li, M; Sharma, A; Tan, X; Xiao, Y; Yin, C, 2017)
" In the present study, we investigated the potential therapeutic effects of metformin (Met) and saxagliptin (Saxa), as insulin sensitizing agents, in a rat model of brain aging and AD using D-galactose (D-gal, 150 mg/kg/day, s."3.85Involvement of insulin resistance in D-galactose-induced age-related dementia in rats: Protective role of metformin and saxagliptin. ( Attia, A; El-Shenawy, S; Gomaa, N; Hassan, A; Hegazy, R; Kenawy, S; Zaki, H, 2017)
" We hypothesized that co-administration of SB extract and metformin exerts a better effect on obesity-induced insulin resistance and lipid metabolism than treatment with metformin alone."3.85In vivo therapeutic effect of combination treatment with metformin and Scutellaria baicalensis on maintaining bile acid homeostasis. ( Bose, S; Chin, YW; Choi, HS; Han, K; Kim, H; Kim, YM; Lim, SK; Wang, JH, 2017)
"We aim to assess the effects of metformin treatment on metabolic and endocrine parameters and genes expression related to the insulin-responsive pathway in polycystic ovary syndrome (PCOS)."3.85IGF-1R and Leptin Expression Profile and the Effects of Metformin Treatment on Metabolic and Endocrine Parameters in PCOS Mice. ( Abi Haidar, M; Berguio Vidotti, D; de Almeida, BC; de Jesus Simões, M; Prado Correia, LE; Silva, I, 2017)
" We evaluated whether obesity exacerbates progression of endometrial hyperplasia (EH) using the PRCre/+ PTENflox/+ mouse model and examined if the type 2 diabetes drug, metformin, could prevent EH."3.85Lean Body Weight and Metformin Are Insufficient to Prevent Endometrial Hyperplasia in Mice Harboring Inactivating Mutations in PTEN. ( Celestino, J; Iglesias, DA; Lu, KH; Schmandt, RE; Sun, CC; Yates, MS; Zhang, Q, 2017)
" In the present study, the effects of metformin on the development and recurrence of hepatocellular carcinoma (HCC) were investigated using the diethylnitrosamine (DEN)‑induced rat model of HCC."3.83Metformin inhibits early stage diethylnitrosamine‑induced hepatocarcinogenesis in rats. ( Chang, M; Choi, HJ; Jang, JJ; Jang, S; Jo, W; Lee, HJ; Park, HK; Ryu, JE; Son, WC; Yu, ES, 2016)
"Metformin reduces body weight by decreasing food intake in humans and animals."3.83The effect of metformin on neuronal activity in the appetite-regulating brain regions of mice fed a high-fat diet during an anorectic period. ( Choi, SH; Jin, BY; Kim, DH; Kim, HJ; Oh, MJ; Shin, KH, 2016)
"Canagliflozin 100 and 300 mg provided sustained reductions in body weight, BMI, and waist circumference in a greater proportion of patients with T2DM versus glimepiride or placebo over 104 weeks."3.83Effects of canagliflozin on body weight and body composition in patients with type 2 diabetes over 104 weeks. ( Blonde, L; Canovatchel, W; Fung, A; Meininger, G; Stenlöf, K; Xie, J, 2016)
"To investigate changes in body weight trajectories after the addition of individual sulphonylureas (SUs) to metformin in patients with type 2 diabetes."3.83Addition of sulphonylurea to metformin does not relevantly change body weight: a prospective observational cohort study (ZODIAC-39). ( Bilo, HJ; de Bock, GH; Groenier, KH; Houweling, ST; Kleefstra, N; Landman, GW; Schrijnders, D; van Hateren, KJ; Wever, R, 2016)
"We investigated the effects of metformin and celecoxib on obesity-induced adipose tissue inflammation, insulin resistance (IR), fatty liver, and high blood pressure in high-fat (HF) fed rats."3.83Additional effect of metformin and celecoxib against lipid dysregulation and adipose tissue inflammation in high-fat fed rats with insulin resistance and fatty liver. ( Hsieh, PS; Hung, YJ; Lu, CH, 2016)
" This study is to investigate the role of apoA5 in obesity-associated hypertriglyceridemia and metformin-related hypotriglyceridemic actions."3.83Metformin ameliorates obesity-associated hypertriglyceridemia in mice partly through the apolipoprotein A5 pathway. ( Chen, LZ; Huang, XS; Li, R; Zhao, SP; Zhao, W, 2016)
"The methanol (MECR) and aqueous (AECR) extracts (200 and 400mg/kg body weight) were administered orally to normal and diabetic rats with Metformin and solvent control as comparison groups."3.83Antidiabetic effects of Cuscuta reflexa Roxb. in streptozotocin induced diabetic rats. ( Kar, DM; Maharana, L; Panigrahi, SK; Rath, D, 2016)
"The children of mothers with GDM randomised to metformin (n = 47) or insulin (n = 50) treatment during pregnancy."3.81A follow-up of a randomised study of metformin and insulin in gestational diabetes mellitus: growth and development of the children at the age of 18 months. ( Ijäs, H; Keravuo, R; Raudaskoski, T; Saarela, T; Vääräsmäki, M, 2015)
"To determine the effects of metformin therapy in children with metabolic syndrome (MS)."3.81Metformin treatment improves weight and dyslipidemia in children with metabolic syndrome. ( Ashraf, AP; Luong, DQ; Oster, R, 2015)
" We hypothesized that neonatal treatment with antidiabetic drug biguanide metformin would positively modify regulation of growth hormone--IGF-1--insulin signaling pathway slowing down aging and improving cancer preventive patterns in rodents."3.81Sex differences in aging, life span and spontaneous tumorigenesis in 129/Sv mice neonatally exposed to metformin. ( Anisimov, VN; Egormin, PA; Khaitsev, NV; Panchenko, AV; Popovich, IG; Semenchenko, AV; Trashkov, AP; Tyndyk, ML; Vasiliev, AG; Yurova, MN; Zabezhinski, MA, 2015)
"Metformin treatment is associated with a decreased risk and better prognosis of pancreatic cancer (PC) in patients with type 2 diabetes, but the mechanism of metformin's PC growth inhibition in the context of a prediabetic state is unknown."3.81Metformin and Rapamycin Reduce Pancreatic Cancer Growth in Obese Prediabetic Mice by Distinct MicroRNA-Regulated Mechanisms. ( Cifarelli, V; Devlin, KL; Dunlap, SM; Huang, J; Hursting, SD; Kaaks, R; Lashinger, LM; Pollak, MN, 2015)
" Metformin is a first-line treatment of type 2 diabetes, with minimal weight loss in humans."3.81Synergistic Effects of a GPR119 Agonist with Metformin on Weight Loss in Diet-Induced Obese Mice. ( Al-Barazanji, K; Benson, W; Binz, J; Chen, L; Generaux, C; McNulty, J; Young, A, 2015)
"Sixty six adult patients with schizophrenia or schizoaffective disorder treated, with atypical antipsychotics, and who had increased by more than 10% their pre treatment body weight, were randomly assigned to receive metformin or placebo in a double-blind study."3.81Metformin for treatment of antipsychotic-induced weight gain in a South Asian population with schizophrenia or schizoaffective disorder: A double blind, randomized, placebo controlled study. ( Dayabandara, M; de Silva, VA; Gunewardena, H; Hanwella, R; Henegama, T; Suraweera, C; Wijesundara, H, 2015)
"Metformin decreases polycystic ovary syndrome (PCOS) symptoms, induces ovulation, and may improve developmental competence of in vitro oocyte maturation."3.81Does metformin improve in vitro maturation and ultrastructure of oocytes retrieved from estradiol valerate polycystic ovary syndrome-induced rats. ( Mesbah, F; Mirkhani, H; Moslem, M; Vojdani, Z, 2015)
"The aim of our study was to assess the value of blood pressure and heart rate using the 24-hour blood pressure monitoring (ABPM) before and after treatment with metformin to patients with polycystic ovary syndrome (PCOS) and normal lean."3.81[Metformin and changes in blood pressure and heart rate in lean patients with polycystic ovary syndrome (PCOS)--preliminary study]. ( Kiałka, M; Klocek, M; Kowalczuk, A; Migacz, K; Milewicz, T; Ociepka, A; Tomczyk, R, 2015)
"In the present study, the ability of metformin to inhibit skin tumor promotion by 12-O-tetradecanoylphorbol-13-acetate (TPA) was analyzed in mice maintained on either an overweight control diet or an obesity-inducing diet."3.80Metformin inhibits skin tumor promotion in overweight and obese mice. ( Angel, JM; Beltran, L; Blando, J; Checkley, LA; Cho, J; DiGiovanni, J; Hursting, SD; Rho, O, 2014)
"Over a 20-year period, patients on dapagliflozin were projected to experience relative reductions in the incidence of myocardial infarction (MI), stroke, CV death, and all-cause death of 13."3.80Modeling effects of SGLT-2 inhibitor dapagliflozin treatment versus standard diabetes therapy on cardiovascular and microvascular outcomes. ( Alperin, P; Cohen, M; Dziuba, J; Goswami, D; Grossman, HL; Hardy, E; Iloeje, U; Perlstein, I; Racketa, J, 2014)
"Danish individuals without prior myocardial infarction or stroke that initiated combinations of metformin with sulphonylurea (SU), DPP-4 inhibitors, GLP-1 agonists or insulin between 9 May 2007 and 31 December 2011 were followed up for the risk of all-cause mortality, cardiovascular (CV) mortality or a combined end point of myocardial infarction, stroke and CV mortality."3.80Cardiovascular safety of combination therapies with incretin-based drugs and metformin compared with a combination of metformin and sulphonylurea in type 2 diabetes mellitus--a retrospective nationwide study. ( Andersson, C; Fosbøl, EL; Gislason, G; Køber, L; Mogensen, UM; Scheller, NM; Schramm, TK; Torp-Pedersen, C; Vaag, A, 2014)
"Metformin could retard body weight gain, improve insulin sensitivity and reduce intramyocellular lipid accumulation in ob/ob mice."3.80Metformin suppresses lipid accumulation in skeletal muscle by promoting fatty acid oxidation. ( Hu, P; Li, Q; Li, Z; Liu, F; Wang, C; Wang, H; Wu, J; Ye, J; Yuan, Y; Zhang, L, 2014)
"Metformin is commonly used as the first line of medication for the treatment of metabolic syndromes, such as obesity and type 2 diabetes (T2D)."3.80Effect of metformin on metabolic improvement and gut microbiota. ( Ko, G; Lee, H, 2014)
"Elevated asymmetric dimethylarginine (ADMA) levels and nitric oxide (NO) deficiency are associated with the development of hypertension."3.80Metformin reduces asymmetric dimethylarginine and prevents hypertension in spontaneously hypertensive rats. ( Hsu, CN; Huang, LT; Kuo, HC; Tain, YL; Tsai, CM, 2014)
"Metformin administration resulted in significant decrease in the body weight, body mass index, hirsutism score, fasting and postprandial blood glucose, fasting serum insulin, HOMA index, sleep disturbances scale, and Epworth sleepiness scale compared to the untreated PCOS group."3.80Effect of metformin on sleep disorders in adolescent girls with polycystic ovarian syndrome. ( Abdelmotaleb, GS; Aly, MK; El-Sharkawy, AA; Kabel, AM, 2014)
"The antidiabetic drug metformin is currently used prior and during pregnancy for polycystic ovary syndrome, as well as during gestational diabetes mellitus."3.79Prenatal metformin exposure in mice programs the metabolic phenotype of the offspring during a high fat diet at adulthood. ( Ailanen, L; Ilyasizadeh, J; Jäppinen, NT; Koulu, M; Laurila, K; Penttinen, AM; Pesonen, U; Salomäki, H; Vähätalo, LH, 2013)
"Obesity is becoming a health concern worldwide and metformin, a first line anti-diabetic drug, was associated with weight loss under different backgrounds."3.79Effect of metformin on the urinary metabolites of diet-induced-obese mice studied by ultra performance liquid chromatography coupled to time-of-flight mass spectrometry (UPLC-TOF/MS). ( Cong, W; Feng, Y; Ruan, K; Shen, L; Wang, B; Xu, D; Zhu, Y, 2013)
"Telmisartan acts beneficially against diabetes-induced inflammation and improves insulin resistance in pre-diabetes OLETF rats fed with HFD."3.79Angiotensin II receptor blocker telmisartan prevents new-onset diabetes in pre-diabetes OLETF rats on a high-fat diet: evidence of anti-diabetes action. ( Li, LY; Luo, R; Sun, LT; Tian, FS; Xiong, HL; Zhao, ZQ; Zheng, XL, 2013)
" As a result of the proposed method of treatment had improved the clinical course of CCH due to lower body weight, body mass index (BMI) and abdominal obesity indexes (AOI), which were characterized by decreasing the duration and frequency of angina attacks, reducing the number of nitroglycerin tablets taken, and also increased exercise tolerance (ET)."3.79[Оptimization of stable angina standard therapy in patients with concomitant osteoarthritis and obesity]. ( Teslenko, IuV, 2013)
"Gemfibrozil is a PPAR-α ligand that inhibits the progression of atherosclerosis in insulin resistance type 2 diabetes mellitus (IR type 2 DM)."3.79Gemfibrozil and its combination with metformin on pleiotropic effect on IL-10 and adiponectin and anti-atherogenic treatment in insulin resistant type 2 diabetes mellitus rats. ( Kurmi, MK; Raikwar, SK; Sharma, AK; Srinivasan, BP, 2013)
"Metformin is widely used to treat obese diabetics because of its beneficial effects on body weight, energy intake, and glucose regulation."3.79Metformin decreases meal size and number and increases c-Fos expression in the nucleus tractus solitarius of obese mice. ( Choi, SH; Chun, BG; Kim, DH; Kim, HJ; Park, EY; Shin, KH; Zhang, XH, 2013)
"The pharmacokinetics of metformin was influenced by lean body weight on an allometric basis and was related to markers of renal function, age, and serum creatinine in this population of 105 patients."3.78Population pharmacokinetics of metformin in obese and non-obese patients with type 2 diabetes mellitus. ( Bardin, C; Chast, F; Larger, E; Nobecourt, E; Treluyer, JM; Urien, S, 2012)
" Furthermore, the body weight, liver glycogen formation, antioxidant substance (GSH) and antioxidant enzyme (SOD and GPX) levels increased evidently in diabetic mice treated with both ASP and metformin."3.78Anti-diabetic activities of Acanthopanax senticosus polysaccharide (ASP) in combination with metformin. ( Fu, G; Fu, J; Gao, B; Tu, Y; Yuan, J; Zhang, N; Zhang, Y, 2012)
"After 6 weeks treatment, metformin reduced the body weight gain and enhanced insulin sensitivity of high-fat fed rats."3.78Downregulation of chemerin and alleviation of endoplasmic reticulum stress by metformin in adipose tissue of rats. ( Ao, N; Du, J; Liu, H; Pei, L; Yang, J; Zhang, Y, 2012)
" At the end of the feeding schedule, Dia group had insulin resistance along with increased blood glucose, triglyceride, uric acid and nitric oxide (NO) levels."3.78Attenuation of insulin resistance, metabolic syndrome and hepatic oxidative stress by resveratrol in fructose-fed rats. ( Bagul, PK; Banerjee, SK; Bastia, T; Chakravarty, S; Madhusudana, K; Matapally, S; Middela, H; Padiya, R; Reddy, BR, 2012)
" We hypothesised that intervention with metformin would diminish the HF-feeding-evoked cognitive deficit by improving insulin sensitivity."3.78A high-fat-diet-induced cognitive deficit in rats that is not prevented by improving insulin sensitivity with metformin. ( Balfour, DJ; McNeilly, AD; Stewart, CA; Sutherland, C; Williamson, R, 2012)
"To define the pharmacogenetic features of the effect of metformin in coronary heart disease (CHD) patients with metabolic syndrome (MS) or type 2 diabetes mellitus (T2DM), by taking into consideration PPAR-gamma2 Pro1 2Ala polymorphism."3.78[Pharmacogenetic features of the effect of metformin in patients with coronary heart disease in the presence of metabolic syndrome and type 2 diabetes mellitus in terms of PPAR-gamma2 gene polymorphism]. ( Kaĭdashev, IP; Kutsenko, LA; Lavrenko, AV; Mamontova, TV; Shlykova, OA, 2012)
" Metformin treatment improved the insulin sensitivity, and normalized the in vitro bladder hypercontractility and cystometric dysfunction in obese mice."3.78Role of PKC and CaV1.2 in detrusor overactivity in a model of obesity associated with insulin resistance in mice. ( Anhê, GF; Antunes, E; Calixto, MC; De Nucci, G; Grant, AD; Leiria, LO; Lintomen, L; Mónica, FZ; Sollon, C; Zanesco, A, 2012)
" We studied the metabolic effects of treatment with mildronate, metformin and a combination of the two in the Zucker rat model of obesity and impaired glucose tolerance."3.77Anti-diabetic effects of mildronate alone or in combination with metformin in obese Zucker rats. ( Cirule, H; Dambrova, M; Liepinsh, E; Makrecka, M; Skapare, E; Svalbe, B, 2011)
" The chronic treatment of inbred 129/Sv mice with metformin (100 mg/kg in drinking water) slightly modified the food consumption but failed to influence the dynamics of body weight, decreased by 13."3.76Gender differences in metformin effect on aging, life span and spontaneous tumorigenesis in 129/Sv mice. ( Anisimov, VN; Berstein, LM; Egormin, PA; Kovalenko, IG; Piskunova, TS; Popovich, IG; Poroshina, TE; Rosenfeld, SV; Semenchenko, AV; Tyndyk, ML; Yurova, MV; Zabezhinski, MA, 2010)
" We followed the spontaneous evolution of liver steatosis and tested the therapeutic usefulness of metformin and fenofibrate in a model of steatosis, the Zucker diabetic fatty (ZDF) rat."3.75Nonalcoholic hepatic steatosis in Zucker diabetic rats: spontaneous evolution and effects of metformin and fenofibrate. ( Abdallah, P; Basset, A; Beylot, M; del Carmine, P; Forcheron, F; Haffar, G, 2009)
"Women with GDM treated with metformin and with similar baseline risk factors for adverse pregnancy outcomes had less weight gain and improved neonatal outcomes compared with those treated with insulin."3.75Pregnancy outcomes in women with gestational diabetes treated with metformin or insulin: a case-control study. ( Balani, J; Hyer, SL; Rodin, DA; Shehata, H, 2009)
" These mice also have enhanced inflammatory responses to ozone, a common air pollutant that exacerbates asthma."3.74No effect of metformin on the innate airway hyperresponsiveness and increased responses to ozone observed in obese mice. ( Shore, SA; Williams, ES; Zhu, M, 2008)
" Here we show the chronic treatment of female outbred SHR mice with metformin (100 mg/kg in drinking water) slightly modified the food consumption but decreased the body weight after the age of 20 months, slowed down the age-related switch-off of estrous function, increased mean life span by 37."3.74Metformin slows down aging and extends life span of female SHR mice. ( Anisimov, VN; Berstein, LM; Egormin, PA; Kovalenko, IG; Piskunova, TS; Popovich, IG; Poroshina, TE; Semenchenko, AV; Tyndyk, ML; Yurova, MV; Zabezhinski, MA, 2008)
"The objective of this study was to quantify 1-year weight gain associated with the initiation of sulphonylurea (SU), metformin, insulin and thiazolidinedione (TZD) therapy in a representative real world population of type 2 diabetic patients."3.74Weight changes following the initiation of new anti-hyperglycaemic therapies. ( Gomez-Caminero, A; Nichols, GA, 2007)
"The effect of 6 months of metformin treatment was prospectively assessed in 188 PCOS patients, divided into three groups according to body mass index (BMI; lean: BMI<25 kg/m2, overweight: BMI 25-29 kg/m2, and obese: BMI30 kg/m2)."3.74Metformin improves polycystic ovary syndrome symptoms irrespective of pre-treatment insulin resistance. ( Benson, S; Dietz, T; Elsenbruch, S; Hahn, S; Janssen, OE; Kimmig, R; Lahner, H; Mann, K; Moeller, LC; Schmidt, M; Tan, S, 2007)
"The aim of the present study was to evaluate the effect of metformin in very obese subjects with acanthosis nigricans."3.71Therapeutic approach in insulin resistance with acanthosis nigricans. ( Dakovska, L; Kirilov, G; Koev, D; Tankova, T, 2002)
"After adding metformin to the insulin regimen of type 2 diabetics after three months a statistically significant drop of body weight and the daily insulin dose occurred."3.71[Short-term and long-term effect of metformin in type 1 diabetics]. ( Cechurová, D; Jankovec, Z; Kárová, R; Kyselová, P; Lacigová, S; Rusavý, Z, 2001)
"55 g/d for 28 weeks) would ameliorate morbid obesity and reduce centripetal obesity; lipid and lipoprotein cholesterol, insulin, and leptin levels; and plasminogen activator inhibitor activity (PAI-Fx), risk factors for coronary heart disease (CHD)."3.71Metformin reduces weight, centripetal obesity, insulin, leptin, and low-density lipoprotein cholesterol in nondiabetic, morbidly obese subjects with body mass index greater than 30. ( Fontaine, RN; Glueck, CJ; Illig, E; Lang, JE; McCullough, P; Sieve-Smith, L; Streicher, P; Subbiah, MT; Tracy, TM; Wang, P; Weber, K, 2001)
"To evaluate the long-term effects of metformin on biochemical variables and body weight in polycystic ovary syndrome (PCOS)."3.71Biochemical and body weight changes with metformin in polycystic ovary syndrome. ( Batukan, C; Batukan, M; Baysal, B, 2001)
"Before metformin therapy, after covariance adjustment for age, the two cohorts did not differ in height, weight, basal metabolic index, insulin, insulin resistance, or insulin secretion."3.71Metformin therapy throughout pregnancy reduces the development of gestational diabetes in women with polycystic ovary syndrome. ( Glueck, CJ; Kobayashi, S; Phillips, H; Sieve-Smith, L; Wang, P, 2002)
"HCl and metformin on diabetes and obesity were investigated in Wistar fatty rats, which are hyperglycaemic and hypertriglyceridaemic and have higher plasma levels of total ketone bodies than lean rats."3.71Effects of combined pioglitazone and metformin on diabetes and obesity in Wistar fatty rats. ( Ikeda, H; Odaka, H; Sugiyama, Y; Suzuki, M; Suzuki, N, 2002)
" The aim was to define the insulin-sensitizing effects of S15261, the cleavage products, and troglitazone and metformin in the JCR:LA-cp rat, an animal model of the obesity/insulin resistance syndrome that exhibits an associated vasculopathy and cardiovascular disease."3.70Beneficial insulin-sensitizing and vascular effects of S15261 in the insulin-resistant JCR:LA-cp rat. ( Brindley, DN; Davidge, ST; Delrat, P; Jochemsen, R; Kelly, SE; O'Brien, SF; Pégorier, JP; Ravel, D; Russell, JC, 2000)
"The hypothalamic neuropeptide Y content and preproneuropeptide Y mRNA expression were studied in metformin-treated (300 mg/kg orally for 12 days), in pair-fed and in ad libitum-fed obese Zucker rats in order to elucidate possible mechanisms involved in the anorectic and body weight reducing effect of chronic metformin treatment in genetically obese Zucker rats."3.69Anorectic effect of metformin in obese Zucker rats: lack of evidence for the involvement of neuropeptide Y. ( Huupponen, R; Jhanwar-Uniyal, M; Koulu, M; Pesonen, U; Rouru, J; Rouvari, T; Santti, E; Virtanen, K, 1995)
"To determine the relationship between hyperinsulinemia and hypertension in spontaneously hypertensive rats (SHR), the antihyperglycemic agent metformin was administered to SHR and their Wistar-Kyoto (WKY) controls, and its effects on plasma insulin levels and blood pressure were examined."3.69Metformin decreases plasma insulin levels and systolic blood pressure in spontaneously hypertensive rats. ( Bhanot, S; McNeill, JH; Verma, S, 1994)
"To determine whether improvement of insulin resistance decreases blood pressure as well as obesity, metformin (100 mg/kg/d) or vehicle was administered for 20 weeks to 12-week-old male Otsuka Long-Evans Tokushima Fatty (OLETF) rats (n = 10 each), a newly developed animal model of non-insulin-dependent diabetes mellitus (NIDDM) with mild obesity, hyperinsulinemia, and hypertriglyceridemia."3.69Metformin decreases blood pressure and obesity in OLETF rats via improvement of insulin resistance. ( Inukai, K; Ishii, J; Kashiwabara, H; Katayama, S; Kikuchi, C; Kosegawa, I; Negishi, K; Oka, Y, 1996)
"A retrospective analysis was conducted to determine the effects of metformin on glycosylated hemoglobin (HbA1c), body weight, and adverse events in an African-American population."3.69A retrospective analysis of the efficacy and safety of metformin in the African-American patient. ( Anderson, D; Briscoe, TA; Cooper, GS; Usifo, OS, 1997)
"The effect of metformin on glucose metabolism was examined in eight obese (percent ideal body weight, 151 +/- 9%) and six lean (percent ideal body weight, 104 +/- 4%) noninsulin-dependent diabetic (NIDD) subjects before and after 3 months of metformin treatment (2."3.68Mechanism of metformin action in obese and lean noninsulin-dependent diabetic subjects. ( Barzilai, N; DeFronzo, RA; Simonson, DC, 1991)
"In people with type 2 diabetes on metformin, 26-week treatment with iGlarLixi resulted in a marked improvement in β-cell function concomitant with sparing of endogenous insulin release and a reduction in meal absorption."3.11Fixed-ratio combination of insulin glargine plus lixisenatide (iGlarLixi) improves ß-cell function in people with type 2 diabetes. ( Dex, T; Ferrannini, E; Mari, A; Niemoeller, E; Servera, S, 2022)
" Consistent with the GLP-1 RA class, gastrointestinal adverse events were most commonly reported; these were generally transient and mild/moderate in severity."3.11Efficacy and Safety of Once-Weekly Efpeglenatide Monotherapy Versus Placebo in Type 2 Diabetes: The AMPLITUDE-M Randomized Controlled Trial. ( Baek, S; Choi, J; Frias, JP; Muehlen-Bartmer, I; Niemoeller, E; Popescu, L; Rosenstock, J, 2022)
" There was no significant difference in the rate of adverse events for tirzepatide 15 mg, oral-semaglutide 14 mg, and semaglutide 1."3.01Comparison of the efficacy and safety of 10 glucagon-like peptide-1 receptor agonists as add-on to metformin in patients with type 2 diabetes: a systematic review. ( Chen, J; Gu, H; Hu, J; Li, M; Xie, Z, 2023)
"Type 2 diabetes mellitus is closely related to nonalcoholic fatty liver disease(NAFLD)."2.94Liraglutide or insulin glargine treatments improves hepatic fat in obese patients with type 2 diabetes and nonalcoholic fatty liver disease in twenty-six weeks: A randomized placebo-controlled trial. ( Guo, W; Lin, L; Tian, W; Xu, X, 2020)
"Metformin led to an increase in AMPK signaling, and a trend for blunted increases in mTORC1 signaling in response to PRT."2.90Metformin blunts muscle hypertrophy in response to progressive resistance exercise training in older adults: A randomized, double-blind, placebo-controlled, multicenter trial: The MASTERS trial. ( Bamman, MM; Bush, HM; Dungan, CM; Kern, PA; Kosmac, K; Long, DE; McGwin, G; Ovalle, F; Peck, BD; Peterson, CA; Tuggle, SC; Villasante Tezanos, AG; Walton, RG; Windham, ST, 2019)
"More dapagliflozintreated than saxagliptin-treated patients achieved the composite endpoint of HbA1c reduction ≥ 0."2.87Dapagliflozin versus saxagliptin as add-on therapy in patients with type 2 diabetes inadequately controlled with metformin. ( Chen, H; Garcia-Sanchez, R; Mathieu, C; Rosenstock, J; Saraiva, GL, 2018)
"Prediabetes is associated with increased prevalence of cardiovascular disease (CVD)."2.87Effect of intensive lifestyle modification & metformin on cardiovascular risk in prediabetes: A pilot randomized control trial. ( Bantwal, G; Fathima, S; George, B; Kulkarni, S; Umesh, S; Xavier, D, 2018)
"The Treatment Options for type 2 Diabetes in Adolescents and Youth (TODAY) clinical trial documented that metformin plus rosiglitazone, but not metformin plus lifestyle intervention, provided superior durability of glycemic control relative to metformin monotherapy."2.84Weight change in the management of youth-onset type 2 diabetes: the TODAY clinical trial experience. ( El Ghormli, L; Hirst, K; Ievers-Landis, CE; Linder, B; Marcus, MD; van Buren, DJ; Walders-Abramson, N; Wilfley, DE; Zeitler, P, 2017)
"Metformin-treated patients with T2DM also have higher fasted GLP-1 levels, independently of weight and glycaemia."2.84Sustained influence of metformin therapy on circulating glucagon-like peptide-1 levels in individuals with and without type 2 diabetes. ( Dawed, A; Dekker, J; Franks, PW; Hansen, TH; Heggie, A; Holman, RR; Jones, AG; Koivula, R; Pearson, ER; Preiss, D; Sattar, N; Stewart, C; Walker, M; Welsh, P, 2017)
"To assess the effect of metformin versus placebo both in combination with insulin analogue treatment on changes in carotid intima-media thickness (IMT) in patients with type 2 diabetes."2.82Metformin versus placebo in combination with insulin analogues in patients with type 2 diabetes mellitus-the randomised, blinded Copenhagen Insulin and Metformin Therapy (CIMT) trial. ( Almdal, TP; Boesgaard, TW; Breum, L; Carstensen, B; Duun, E; Gade-Rasmussen, B; Gluud, C; Hedetoft, C; Hemmingsen, B; Jensen, T; Krarup, T; Lund, SS; Lundby-Christensen, L; Madsbad, S; Mathiesen, ER; Pedersen, O; Perrild, H; Røder, M; Sneppen, SB; Snorgaard, O; Tarnow, L; Thorsteinsson, B; Vaag, A; Vestergaard, H; Wetterslev, J; Wiinberg, N, 2016)
"Participants with type 2 diabetes (glycated haemoglobin (HbA1c) ≥ 7."2.82Effects of biphasic, basal-bolus or basal insulin analogue treatments on carotid intima-media thickness in patients with type 2 diabetes mellitus: the randomised Copenhagen Insulin and Metformin Therapy (CIMT) trial. ( Almdal, TP; Boesgaard, TW; Breum, L; Carstensen, B; Duun, E; Gade-Rasmussen, B; Gluud, C; Hedetoft, C; Hemmingsen, B; Jensen, T; Krarup, T; Lund, SS; Lundby-Christensen, L; Madsbad, S; Mathiesen, ER; Pedersen, O; Perrild, H; Røder, M; Sneppen, SB; Snorgaard, O; Tarnow, L; Thorsteinsson, B; Vaag, A; Vestergaard, H; Wetterslev, J; Wiinberg, N, 2016)
" The mean terminal half-life (t1/2 ) was 2-3 h."2.82Safety, tolerability, pharmacokinetics and pharmacodynamics of AZP-531, a first-in-class analogue of unacylated ghrelin, in healthy and overweight/obese subjects and subjects with type 2 diabetes. ( Abribat, T; Allas, S; Delale, T; Julien, M; Ngo, N; Ritter, J; Sahakian, P; van der Lely, AJ, 2016)
"After run-in on metformin and basal-bolus insulin (BBI), 102 participants continued metformin and basal insulin and were randomized to exenatide dosing before the two largest meals (glucacon-like peptide-1 receptor agonist and insulin [GLIPULIN group]) or continuation of rapid-acting insulin analogs (BBI group)."2.82Glucose Variability in a 26-Week Randomized Comparison of Mealtime Treatment With Rapid-Acting Insulin Versus GLP-1 Agonist in Participants With Type 2 Diabetes at High Cardiovascular Risk. ( , 2016)
"LixiLan achieved statistically significant reductions to near-normal HbA1c levels with weight loss and no increased hypoglycemic risk, compared with insulin glargine alone, and a low incidence of gastrointestinal adverse events in type 2 diabetes inadequately controlled on metformin."2.82Efficacy and Safety of LixiLan, a Titratable Fixed-Ratio Combination of Lixisenatide and Insulin Glargine, Versus Insulin Glargine in Type 2 Diabetes Inadequately Controlled on Metformin Monotherapy: The LixiLan Proof-of-Concept Randomized Trial. ( Aroda, VR; Diamant, M; Fonseca, V; Perfetti, R; Rosenstock, J; Silvestre, L; Souhami, E; Zhou, T, 2016)
"This multicenter, double-blind, placebo-controlled study examined the efficacy and safety of ipragliflozin, a sodium-glucose co-transporter 2 inhibitor, in combination with metformin in Japanese patients with type 2 diabetes mellitus (T2DM)."2.80Ipragliflozin in combination with metformin for the treatment of Japanese patients with type 2 diabetes: ILLUMINATE, a randomized, double-blind, placebo-controlled study. ( Goto, K; Kashiwagi, A; Kazuta, K; Ueyama, E; Utsuno, A; Yoshida, S, 2015)
"To evaluate the efficacy and safety of twice-daily dosing of dapagliflozin and metformin, exploring the feasibility of a fixed-dose combination."2.80Twice-daily dapagliflozin co-administered with metformin in type 2 diabetes: a 16-week randomized, placebo-controlled clinical trial. ( Burgess, L; de Bruin, TW; Hamer-Maansson, JE; Hruba, V; Korányi, L; Schumm-Draeger, PM, 2015)
" Changes in HbA1c level, fasting plasma glucose and body weight, as well as adverse events, were assessed over 102 weeks."2.80Efficacy and safety of dapagliflozin monotherapy in people with Type 2 diabetes: a randomized double-blind placebo-controlled 102-week trial. ( Bailey, CJ; List, JF; Morales Villegas, EC; Ptaszynska, A; Tang, W; Woo, V, 2015)
"People with insulin-requiring type 2 diabetes and high cardiovascular risk were enrolled during a run-in period on basal-bolus insulin (BBI), and 102 were randomized to continued BBI or to basal insulin with a prandial GLP-1 receptor agonist (GLIPULIN) group, each seeking to maintain HbA(1c) levels between 6."2.80Design of FLAT-SUGAR: Randomized Trial of Prandial Insulin Versus Prandial GLP-1 Receptor Agonist Together With Basal Insulin and Metformin for High-Risk Type 2 Diabetes. ( Bergenstal, R; Branch, KR; Davis, B; Hirsch, I; Khakpour, D; Kingry, C; O'Brien, K; Pressel, S; Probstfield, JL; Riddle, M, 2015)
"Metformin plays an important role in diabetes treatment."2.80The Efficacy and Safety of Chinese Herbal Medicine Jinlida as Add-On Medication in Type 2 Diabetes Patients Ineffectively Managed by Metformin Monotherapy: A Double-Blind, Randomized, Placebo-Controlled, Multicenter Trial. ( Chen, X; Guo, J; Li, Z; Lian, F; Ma, L; Piao, C; Tian, J; Tong, X; Wang, CZ; Xia, C; Yuan, CS; Zhao, L, 2015)
"Metformin treatment had no substantial influence on tofogliflozin efficacy."2.80A novel and selective sodium-glucose cotransporter-2 inhibitor, tofogliflozin, improves glycaemic control and lowers body weight in patients with type 2 diabetes mellitus. ( Beck, A; Beyer, U; Boerlin, V; Christ, AD; Ciorciaro, C; Cynshi, O; Ikeda, S; Kadowaki, T; Meyer, M; Takano, Y; Tanaka, R, 2015)
"Patients with type 2 diabetes mellitus (T2DM) using sulphonylurea and metformin received dapagliflozin 10 mg/day or placebo added to therapy for 52 weeks (24-week randomized, double-blind period plus 28-week double-blind extension)."2.80Durability and tolerability of dapagliflozin over 52 weeks as add-on to metformin and sulphonylurea in type 2 diabetes. ( Bowering, K; Johnsson, E; Matthaei, S; Parikh, S; Rohwedder, K; Sugg, J, 2015)
"Among overweight adolescents with type 1 diabetes, the addition of metformin to insulin did not improve glycemic control after 6 months."2.80Effect of Metformin Added to Insulin on Glycemic Control Among Overweight/Obese Adolescents With Type 1 Diabetes: A Randomized Clinical Trial. ( Beck, RW; Bethin, KE; Coffey, JK; DiMeglio, LA; Haller, MJ; Katz, ML; Libman, IM; Miller, KM; Nadeau, KJ; Raman, S; Saenz, AM; Shah, A; Simmons, JH; Tamborlane, WV, 2015)
" Safety and tolerability assessments included adverse events (AEs), hypoglycaemia and body weight."2.79A randomized controlled trial of the efficacy and safety of saxagliptin as add-on therapy in patients with type 2 diabetes and inadequate glycaemic control on metformin plus a sulphonylurea. ( Brook, D; Fisher, SA; Kalra, S; Montanaro, M; Monyak, J; Moses, RG; Sockler, J; Visvanathan, J, 2014)
"0 pmol/kg/min (pkm) and placebo, given by continuous subcutaneous infusion over 3 months in combination with metformin and sulphonylurea (SU), to lower haemoglobin A1c (HbA1c), fasting plasma glucose and weight in 95 type 2 diabetes patients with inadequate glycaemic control."2.79Dose response of continuous subcutaneous infusion of recombinant glucagon-like peptide-1 in combination with metformin and sulphonylurea over 12 weeks in patients with type 2 diabetes mellitus. ( Ehlers, MR; Holst, JJ; Torekov, SS, 2014)
"Dapagliflozin treatment induced glucosuria and markedly lowered fasting plasma glucose."2.79Dapagliflozin improves muscle insulin sensitivity but enhances endogenous glucose production. ( Abdul-Ghani, MA; Daniele, G; DeFronzo, RA; Eldor, R; Fiorentino, TV; Merovci, A; Norton, L; Perez, Z; Solis-Herrera, C; Tripathy, D; Xiong, J, 2014)
" Glycosylated hemoglobin (HbA1c) values, fasting and postprandial blood glucose (FBG and P2BG), body weight, body mass index (BMI), episodes of hypoglycemia and adverse events were evaluated."2.79Efficacy and safety comparison of add-on therapy with liraglutide, saxagliptin and vildagliptin, all in combination with current conventional oral hypoglycemic agents therapy in poorly controlled Chinese type 2 diabetes. ( Ding, M; Li, CJ; Liu, XJ; Yu, DM; Yu, P; Yu, Q; Zhang, QM, 2014)
" Over 52 weeks, nausea, diarrhea, and vomiting were the most common adverse events; incidences were similar between dulaglutide and metformin."2.79Efficacy and safety of dulaglutide monotherapy versus metformin in type 2 diabetes in a randomized controlled trial (AWARD-3). ( Pechtner, V; Pérez Manghi, F; Shurzinske, L; Tofé Povedano, S; Umpierrez, G, 2014)
" Rates of serious adverse events in the albiglutide group were similar to comparison groups."2.79HARMONY 3: 104-week randomized, double-blind, placebo- and active-controlled trial assessing the efficacy and safety of albiglutide compared with placebo, sitagliptin, and glimepiride in patients with type 2 diabetes taking metformin. ( Ahrén, B; Cirkel, DT; Feinglos, MN; Johnson, SL; Perry, C; Stewart, M; Yang, F, 2014)
" Pharmacodynamic parameters were assessed at baseline and at weeks 1 and 12."2.79Effect of the sodium glucose co-transporter 2 inhibitor canagliflozin on plasma volume in patients with type 2 diabetes mellitus. ( Farrell, K; Heise, T; Natarajan, J; Plum-Mörschel, L; Polidori, D; Rothenberg, P; Sha, S; Sica, D; Wang, SS, 2014)
" Adverse events (AE) and hypoglycemia were monitored."2.79Saxagliptin efficacy and safety in patients with type 2 diabetes mellitus stratified by cardiovascular disease history and cardiovascular risk factors: analysis of 3 clinical trials. ( Bryzinski, B; Cook, W; Hirshberg, B; Minervini, G, 2014)
"We recruited 25 patients with type 1 diabetes (mean age 51 ± 10 years, mean disease duration 26 ± 13 years) and 31 insulin-treated type 2 diabetic patients (mean age 66 ± 8 years, mean disease duration 19 ± 9 years), who received sitagliptin with metformin as a fixed-dose combination (50/1000 mg once or twice daily) or sitagliptin (100 mg once daily, if intolerant to metformin) in addition to ongoing insulin therapy for 46 ± 19 weeks and 56 ± 14 weeks, respectively."2.78Sitagliptin as add-on therapy in insulin deficiency: biomarkers of therapeutic efficacy respond differently in type 1 and type 2 diabetes. ( Bartola, LD; Giampietro, C; Giampietro, O; Masoni, MC; Matteucci, E, 2013)
"These data suggest that normal-weight type 2 diabetes patients would derive the same benefits from first-line treatment with metformin as overweight and obese patients, and are not at increased risk of excess weight loss."2.78Impact of baseline BMI on glycemic control and weight change with metformin monotherapy in Chinese type 2 diabetes patients: phase IV open-label trial. ( Guo, X; Hu, R; Ji, L; Li, H; Li, Y; Zhu, Z, 2013)
"Pioglitazone was more effective than glibenclamide in improving inflammation and hepatic steatosis indices."2.78Ultrasonography modifications of visceral and subcutaneous adipose tissue after pioglitazone or glibenclamide therapy combined with rosuvastatin in type 2 diabetic patients not well controlled by metformin. ( D'Angelo, A; Derosa, G; Fogari, E; Maffioli, P; Perrone, T, 2013)
" Dapagliflozin in combination and as monotherapy was dosed at 5 mg (Study 1) and 10 mg (Study 2)."2.77Dapagliflozin, metformin XR, or both: initial pharmacotherapy for type 2 diabetes, a randomised controlled trial. ( Hennicken, D; Henry, RR; List, JF; Marmolejo, MH; Murray, AV; Ptaszynska, A, 2012)
"Glycemic control in type 2 diabetes generally worsens over time, requiring intensification of therapy."2.77Glycemic control over 5 years in 4,900 people with type 2 diabetes: real-world diabetes therapy in a clinical trial cohort. ( Best, JD; Davis, TM; Drury, PL; Keech, AC; Kesäniemi, YA; Pardy, C; Scott, R; Taskinen, MR; Voysey, M, 2012)
"In people with type 2 diabetes, a dipeptidyl peptidase-4 (DPP-4) inhibitor is one choice as second-line treatment after metformin, with basal insulin recommended as an alternative."2.77Insulin glargine versus sitagliptin in insulin-naive patients with type 2 diabetes mellitus uncontrolled on metformin (EASIE): a multicentre, randomised open-label trial. ( Aschner, P; Chan, J; Dain, MP; Echtay, A; Fonseca, V; Owens, DR; Picard, S; Pilorget, V; Wang, E, 2012)
" Average increases in insulin dosage with exenatide and placebo were 13 U/d and 20 U/d."2.76Use of twice-daily exenatide in Basal insulin-treated patients with type 2 diabetes: a randomized, controlled trial. ( Bergenstal, RM; Buse, JB; Glass, LC; Heilmann, CR; Hoogwerf, BJ; Kwan, AY; Lewis, MS; Rosenstock, J, 2011)
" The dosage of acarbose and glibenclamide was 50 mg TID and 2."2.76Effects of acarbose versus glibenclamide on glycemic excursion and oxidative stress in type 2 diabetic patients inadequately controlled by metformin: a 24-week, randomized, open-label, parallel-group comparison. ( Lee, IT; Lee, WJ; Lin, SD; Lin, SY; Sheu, WH; Su, SL; Tseng, YH; Tu, ST; Wang, JS, 2011)
"The objective of this study was to assess the efficacy and safety of metformin at the dosage of 2,500 mg/day in the treatment of obese women with PCOS and also to evaluate its effect on weight, hormones, and lipid profile."2.75Metformin 2,500 mg/day in the treatment of obese women with polycystic ovary syndrome and its effect on weight, hormones, and lipid profile. ( Aghahosseini, M; Aleyaseen, A; Kashani, L; Moddaress-Hashemi, S; Mofid, B; Safdarian, L, 2010)
"Intensive treatment of patients with Type 2 diabetes mellitus (T2DM) from the moment of diagnosis facilitates β-cell recovery."2.75Benefits of self-monitoring blood glucose in the management of new-onset Type 2 diabetes mellitus: the St Carlos Study, a prospective randomized clinic-based interventional study with parallel groups. ( Abad, R; Calle-Pascual, AL; Del Valle, L; Durán, A; Fernández, M; Martín, P; Pérez, N; Runkle, I; Sanz, MF, 2010)
"Few studies have given suggestions on appropriate initiation insulin dosage when combined with oral antidiabetic drugs (OADs)."2.75Appropriate insulin initiation dosage for insulin-naive type 2 diabetes outpatients receiving insulin monotherapy or in combination with metformin and/or pioglitazone. ( Dong, JJ; Liao, L; Mou, YR; Qiu, LL; Yang, M; Zhao, JJ, 2010)
" The incidence of adverse events (AEs), serious AEs and adjudicated cardiovascular events was 74."2.74Fifty-two-week efficacy and safety of vildagliptin vs. glimepiride in patients with type 2 diabetes mellitus inadequately controlled on metformin monotherapy. ( Ahrén, B; Byiers, S; Dejager, S; Ferrannini, E; Fonseca, V; Matthews, D; Shao, Q; Zinman, B, 2009)
"Vildagliptin is an effective and well-tolerated treatment option in elderly patients with type 2 diabetes, demonstrating similar improvement in glycaemic control as metformin, with superior GI tolerability."2.74Comparison of vildagliptin and metformin monotherapy in elderly patients with type 2 diabetes: a 24-week, double-blind, randomized trial. ( Bosi, E; Dejager, S; Schweizer, A, 2009)
"The aim of the study was to compare the efficacy and safety of liraglutide in type 2 diabetes mellitus vs placebo and insulin glargine (A21Gly,B31Arg,B32Arg human insulin), all in combination with metformin and glimepiride."2.74Liraglutide vs insulin glargine and placebo in combination with metformin and sulfonylurea therapy in type 2 diabetes mellitus (LEAD-5 met+SU): a randomised controlled trial. ( Antic, S; Lalic, N; Ravn, GM; Russell-Jones, D; Schmitz, O; Sethi, BK; Simó, R; Vaag, A; Zdravkovic, M, 2009)
"Insulin initiation in patients with type 2 diabetes is often delayed because of concerns about injections."2.74Initiation of prandial insulin therapy with AIR inhaled insulin or insulin lispro in patients with type 2 diabetes: A randomized noninferiority trial. ( Althouse, S; Berclaz, PY; Colon-Vega, G; Ferguson, JA; Gross, JL; Milicevic, Z; Nakano, M; Ortiz-Carasquillo, R; Tobian, JA, 2009)
"Metformin is an oral hypoglycaemic agent that improves insulin action in patients with type-2 diabetes."2.73Effect of adjunct metformin treatment in patients with type-1 diabetes and persistent inadequate glycaemic control. A randomized study. ( Alibegovic, AC; Astrup, AS; Frandsen, M; Hovind, P; Jacobsen, PK; Lund, SS; Parving, HH; Parving, I; Pietraszek, L; Rossing, P; Tarnow, L; Vaag, AA, 2008)
"Twenty-eight patients with type 2 diabetes mellitus (HbAlc>7."2.73Effect of metformin on serum lipoprotein lipase mass levels and LDL particle size in type 2 diabetes mellitus patients. ( Ebisuno, M; Endo, K; Koide, N; Miyashita, Y; Murano, T; Ohira, M; Oyama, T; Saiki, A; Shirai, K; Watanabe, H, 2007)
" Compared with placebo, sitagliptin had a neutral effect on body weight and did not significantly increase the risk of hypoglycemia or gastrointestinal adverse events."2.73Efficacy and safety of sitagliptin added to ongoing metformin therapy in patients with type 2 diabetes. ( Alba, M; Amatruda, JM; Chen, Y; Hussain, S; Kaufman, KD; Langdon, RB; Raz, I; Stein, PP; Wu, M, 2008)
" Both active treatments were generally well tolerated, with no increased risk of hypoglycaemia or gastrointestinal adverse events compared with placebo."2.73Efficacy and safety of sitagliptin when added to ongoing metformin therapy in patients with type 2 diabetes. ( Davies, MJ; Engel, SS; Loeys, T; Scott, R, 2008)
"In patients with type 2 diabetes mellitus (T2DM), biomarkers reflecting inflammation and endothelial dysfunction have been linked to cardiovascular disease (CVD biomarkers) and metabolic regulation."2.73Impact of metformin versus repaglinide on non-glycaemic cardiovascular risk markers related to inflammation and endothelial dysfunction in non-obese patients with type 2 diabetes. ( Frandsen, M; Gram, J; Lund, SS; Parving, HH; Pedersen, O; Schalkwijk, CG; Smidt, UM; Stehouwer, CD; Tarnow, L; Teerlink, T; Vaag, AA; Winther, K, 2008)
"Semaglutide is an advantageous choice for the treatment of T2D since it has greater efficacy in reducing glycated hemoglobin and body weight compared with other GLP-1RAs, has demonstrated benefits in reducing major adverse cardiovascular events, and has a favorable profile in special populations (e."2.72Clinical Perspectives on the Use of Subcutaneous and Oral Formulations of Semaglutide. ( Gallwitz, B; Giorgino, F, 2021)
"In type 2 diabetic patients we compared 9 months of combination therapy with insulin glargine and metformin with 9 months of NPH insulin combined with metformin."2.72Insulin glargine or NPH combined with metformin in type 2 diabetes: the LANMET study. ( Hänninen, J; Hardy, K; Hulme, S; Kauppinen-Mäkelin, R; Lahdenperä, S; Lehtonen, R; Levänen, H; McNulty, S; Nikkilä, K; Ryysy, L; Tiikkainen, M; Tulokas, T; Vähätalo, M; Virtamo, H; Yki-Järvinen, H, 2006)
"Liraglutide is a promising drug for the treatment of type 2 diabetes."2.72Five weeks of treatment with the GLP-1 analogue liraglutide improves glycaemic control and lowers body weight in subjects with type 2 diabetes. ( Filipczak, R; Gumprecht, J; Hompesch, M; Le, TD; Nauck, MA; Zdravkovic, M, 2006)
"Starting insulin in Type 2 diabetes patients with twice-daily BIAsp 30 plus met can reduce HbA (1c) and mean prandial plasma glucose increment to a greater extent than once-daily glarg plus glim."2.72Starting insulin therapy in type 2 diabetes: twice-daily biphasic insulin Aspart 30 plus metformin versus once-daily insulin glargine plus glimepiride. ( Kann, PH; Medding, J; Moeller, J; Mokan, M; Mrevlje, F; Regulski, M; Szocs, A; Wascher, T; Zackova, V, 2006)
"Sibutramine treatment raised sitting diastolic blood pressure by > or = 5 mmHg in a higher proportion of patients than did placebo (43% with 15 mg/day vs."2.71A randomized trial of sibutramine in the management of obese type 2 diabetic patients treated with metformin. ( McNulty, SJ; Ur, E; Williams, G, 2003)
"Mean body weight was unchanged in the rosiglitazone group, while it decreased by 2."2.71Differential effects of rosiglitazone and metformin on adipose tissue distribution and glucose uptake in type 2 diabetic subjects. ( Hällsten, K; Huupponen, R; Janatuinen, T; Knuuti, J; Lönnqvist, F; Lönnroth, P; Nuutila, P; Parkkola, R; Rönnemaa, T; Viljanen, T; Virtanen, KA, 2003)
" Adverse events were reported in only 2."2.71Efficacy, tolerability and safety of nateglinide in combination with metformin. Results from a study under general practice conditions. ( Lehwalder, D; Schandry, R; Schatz, H; Schoppel, K, 2003)
"Thirty-one volunteers with type 2 diabetes mellitus, 16 on dietary therapy and 15 on sulfonylurea monotherapy (SU), were treated with metformin for 12 weeks."2.71Effect of metformin treatment on multiple cardiovascular disease risk factors in patients with type 2 diabetes mellitus. ( Abbasi, F; Chu, JW; Lamendola, C; Leary, ET; McLaughlin, T; Reaven, GM, 2004)
"Weight gain was avoided when MET therapy preceded the addition of TGZ therapy."2.71Improved glycemic control without weight gain using triple therapy in type 2 diabetes. ( Avilés-Santa, ML; Raskin, P; Strowig, SM, 2004)
"Metformin was adjusted up to 2,550 mg/day before insulin therapy was initiated with 5-6 units BIAsp 70/30 twice daily or 10-12 units glargine at bedtime and titrated to target blood glucose (80-110 mg/dl) by algorithm-directed titration."2.71Initiating insulin therapy in type 2 Diabetes: a comparison of biphasic and basal insulin analogs. ( Allen, E; Bode, B; Gabbay, RA; Garber, A; Hollander, P; Hu, P; Lewin, A; Raskin, P, 2005)
"To evaluate the efficacy and safety of two dosage strengths of a single-tablet metformin-glibenclamide (glyburide) combination, compared with the respective monotherapies, in patients with Type 2 diabetes mellitus (DM) inadequately controlled by metformin monotherapy."2.70Improved glycaemic control with metformin-glibenclamide combined tablet therapy (Glucovance) in Type 2 diabetic patients inadequately controlled on metformin. ( Allavoine, T; Howlett, H; Lehert, P; Marre, M, 2002)
"Metformin was tolerated well by the majority of patients."2.70The effects of metformin on body mass index and glucose tolerance in obese adolescents with fasting hyperinsulinemia and a family history of type 2 diabetes. ( Bursey, D; Freemark, M, 2001)
"Therefore, glibenclamide treatment of Type 2 diabetes mellitus may have hazardous cardiovascular effects when used under conditions of ischaemia."2.70Vascular effects of glibenclamide vs. glimepiride and metformin in Type 2 diabetic patients. ( Abbink, EJ; Jansen van Rosendaal, A; Lutterman, JA; Pickkers, P; Russel, FG; Smits, P; Tack, CJ, 2002)
"Obese and overweight type 2 diabetes patients treated with insulin for at least 1 year, and with poor glycaemic control (HbA1c > upper reference level + 2%), were included in a randomised, double-blind, placebo-controlled study."2.70Long-term glycaemic improvement after addition of metformin to insulin in insulin-treated obese type 2 diabetes patients. ( Hermann, LS; Kalén, J; Katzman, P; Lager, I; Nilsson, A; Norrhamn, O; Sartor, G; Ugander, L, 2001)
" In study 2 (n = 14), subjects already established on adjunctive metformin/insulin therapy stopped the metformin component and received 12 weeks of metformin at their baseline dosage (range 1-2."2.69The effects of metformin on glycemic control and serum lipids in insulin-treated NIDDM patients with suboptimal metabolic control. ( Burke, J; Elkeles, RS; Johnston, DG; Robinson, AC; Robinson, S, 1998)
"Defective GS activity in obese NIDDM patients is not secondary to hyperglycemia."2.69Irreversibility of the defect in glycogen synthase activity in skeletal muscle from obese patients with NIDDM treated with diet and metformin. ( Beck-Nielsen, H; Damsbo, P; Hermann, LS; Hother-Nielsen, O; Vaag, A, 1998)
"Metformin is an effective adjunct to insulin therapy in patients with type 2 diabetes."2.69Effects of metformin in patients with poorly controlled, insulin-treated type 2 diabetes mellitus. A randomized, double-blind, placebo-controlled trial. ( Avilés-Santa, L; Raskin, P; Sinding, J, 1999)
"Troglitazone and metformin lower glucose levels in diabetic patients without increasing plasma insulin levels."2.69A comparison of troglitazone and metformin on insulin requirements in euglycemic intensively insulin-treated type 2 diabetic patients. ( Kruszynska, YT; Mulford, MI; Olefsky, JM; Yu, JG, 1999)
" The first three dose levels comprised increasing single-drug therapy (M or G) or primary combination at increasing but low dosage (MGL), and the second three levels were composed of various high-dose combinations, i."2.67Therapeutic comparison of metformin and sulfonylurea, alone and in various combinations. A double-blind controlled study. ( Bitzén, PO; Hermann, LS; Kjellström, T; Lindgärde, F; Melander, A; Scherstén, B, 1994)
"Twenty-two NIDDM patients completed an open randomized cross-over study comparing metformin and glibenclamide over 1 year."2.67Prospective comparative study in NIDDM patients of metformin and glibenclamide with special reference to lipid profiles. ( Hermann, LS; Karlsson, JE; Sjöstrand, A, 1991)
"Metformin was administered and built up to a maximum dosage of 1 g three times daily."2.67Double-blind evaluation of efficacy and tolerability of metformin in NIDDM. ( Dornan, TL; Heller, SR; Peck, GM; Tattersall, RB, 1991)
" The outcomes included changes in HbA1c, FPG, body weight, SBP, DBP and adverse reactions."2.66Efficacy and safety of dapagliflozin plus saxagliptin vs monotherapy as added to metformin in patients with type 2 diabetes: A meta-analysis. ( Li, M; Song, J; Ying, M; Zhuang, Y, 2020)
"Although body weight was unchanged during sulfonylurea/metformin therapy, lean body mass and energy expenditure decreased significantly (p less than 0."2.66Different effects of insulin and oral antidiabetic agents on glucose and energy metabolism in type 2 (non-insulin-dependent) diabetes mellitus. ( Ekstrand, A; Eriksson, J; Franssila-Kallunki, A; Groop, L; Saloranta, C; Schalin, C; Widén, E, 1989)
" Mean initial dosage was 7."2.64Glipizide in the treatment of maturity-onset diabetes: a multi-centre, out-patient study. ( Fowler, LK, 1978)
" The daily dosage of phenformin and metformin was increased at weekly intervals up to 300 mg."2.63Weight-reducing effect of diguanides in obese non-diabetic women. ( Duncan, LJ; MacCuish, AC; Marshall, A; Munro, JF; Wilson, EM, 1969)
"Obesity is one of the main risk factors for type 2 diabetes (T2D), representing a major worldwide health crisis."2.61Body Weight Considerations in the Management of Type 2 Diabetes. ( Apovian, CM; O'Neil, PM; Okemah, J, 2019)
"Dapagliflozin treatment was more cost-effective compared with metformin treatment for Chinese type 2 diabetes patients."2.61Cost-effectiveness analysis of dapagliflozin treatment versus metformin treatment in Chinese population with type 2 diabetes. ( Cai, X; Chen, Y; Gu, S; Ji, L; Nie, L; Shi, L; Yang, W, 2019)
"The majority of patients with type 2 diabetes also have obesity."2.58Understanding the impact of commonly utilized, non-insulin, glucose-lowering drugs on body weight in patients with type 2 diabetes. ( Dunham, MW; Hurren, KM, 2018)
" This meta-analysis revealed the use of dulaglutide as a monotherapy or an add-on to OAM and lispro appeared to be effective and safe for adults with T2DM."2.53Efficacy and safety of dulaglutide in patients with type 2 diabetes: a meta-analysis and systematic review. ( Tong, N; Zhang, L; Zhang, M; Zhang, Y, 2016)
"Most patients with type 2 diabetes, who receive monotherapy, are unable to maintain glucose levels with the progress of disease."2.53Empagliflozin/metformin fixed-dose combination: a review in patients with type 2 diabetes. ( Hu, J; Tan, X; Zhang, S; Zhou, M; Zou, P, 2016)
"Preliminary evidence suggests a dose-response relationship between metformin use and increases in height in children and adolescents compared with a control group."2.52Evaluating the Effects of Metformin Use on Height in Children and Adolescents: A Meta-analysis of Randomized Clinical Trials. ( Boulé, NG; Carson, V; Kuzik, N; Myette-Côté, É; Slater, L, 2015)
" RCTs were selected for meta-analysis if (1) they were RCTs comparing DPP-4 inhibitors plus metformin as initial combination therapy or DPP-4 inhibitor monotherapy to metformin monotherapy, (2) duration of treatment was ≥12 weeks and (3) reported data on haemoglobin A1c (HbA1c) change, fasting plasma glucose (FPG) change, weight change, adverse cardiovascular (CV) events, hypoglycaemia or gastrointestinal adverse events (AEs)."2.50Efficacy and safety of dipeptidyl peptidase-4 inhibitors and metformin as initial combination therapy and as monotherapy in patients with type 2 diabetes mellitus: a meta-analysis. ( Li, L; Liu, C; Wu, D, 2014)
"RCTs enrolling subjects with type 2 diabetes inadequately controlled on metformin monotherapy were included."2.50Dapagliflozin compared with other oral anti-diabetes treatments when added to metformin monotherapy: a systematic review and network meta-analysis. ( Barnett, AH; Goring, S; Hawkins, N; Roudaut, M; Townsend, R; Wood, I; Wygant, G, 2014)
" The glucose-dependency of their glucagon-inhibiting and insulin-enhancing effects, together with their weight-sparing properties, make the incretin therapies a logical proposition for use in combination with exogenous basal insulin therapy."2.49Incretin-based therapy in combination with basal insulin: a promising tactic for the treatment of type 2 diabetes. ( Bain, SC; Damci, T; Dzida, G; Hollander, P; Meneghini, LF; Ross, SA; Vora, J, 2013)
" Longer-acting GLP-1 agonists are dosed less frequently, appear to be associated with less nausea, and may be associated with better rates of adherence than shorter-acting agents."2.47Optimizing outcomes for GLP-1 agonists. ( Freeman, JS, 2011)
"Metformin is a cornerstone of oral antidiabetic treatment."2.45Metformin--the gold standard in type 2 diabetes: what does the evidence tell us? ( Bosi, E, 2009)
"Vildagliptin is a potent and selective inhibitor of dipeptidyl peptidase-IV (DPP-4), orally active, that improves glycemic control in patients with type 2 diabetes (T2DM) primarily by enhancing pancreatic (alpha and beta) islet function."2.44Combination treatment in the management of type 2 diabetes: focus on vildagliptin and metformin as a single tablet. ( Dejager, S; Foley, J; Halimi, S; Minic, B; Schweizer, A, 2008)
"However, many antidiabetic treatments increase body weight."2.44Metformin and body weight. ( Golay, A, 2008)
"Obesity is a chronic metabolic disorder that affects one third of American adults."2.44Pharmacotherapy for obesity. ( Aronne, LJ; Neff, LM, 2007)
"The aim of this study was to quantify the effect of a sulphonylurea on glycaemic control and the risk adverse events when incorporated into the treatment regimen of patients with type 2 diabetes inadequately controlled on metformin."2.44Glycaemic control and adverse events in patients with type 2 diabetes treated with metformin + sulphonylurea: a meta-analysis. ( Belsey, J; Krishnarajah, G, 2008)
"Insulin resistance is a condition in which the glycemic response to insulin is less than normal."2.42Treatment of insulin resistance in diabetes mellitus. ( Banerji, MA; Lebovitz, HE, 2004)
"Metformin has been used for over 40 years as an effective glucose-lowering agent in type 2 (noninsulin-dependent) diabetes mellitus."2.40A risk-benefit assessment of metformin in type 2 diabetes mellitus. ( Bailey, CJ; Howlett, HC, 1999)
"Metformin is a commonly used drug of PCOS but few studies on whether metformin can improve the follicle development and ovarian function in PCOS."1.91Metformin improves polycystic ovary syndrome in mice by inhibiting ovarian ferroptosis. ( Chang, Q; Chen, X; He, R; Hei, C; Li, G; Liang, X; Liu, H; Liu, X; Ouyang, J; Peng, Q; Ren, S; Sun, M; Sun, Y; Wang, C; Wang, Q; Wu, X; Xie, H, 2023)
" The adverse events profile was consistent with other glucagon-like peptide-1 receptor agonists (GLP-1 RAs); gastrointestinal adverse events were most frequent in all three studies."1.91Efficacy and safety of once-weekly efpeglenatide in people with suboptimally controlled type 2 diabetes: The AMPLITUDE-D, AMPLITUDE-L and AMPLITUDE-S randomized controlled trials. ( Aroda, VR; Baek, S; Choi, J; Denkel, K; Espinasse, M; Frias, JP; Guo, H; Ji, L; Lingvay, I; Nguyên-Pascal, ML; Niemoeller, E, 2023)
"We aimed to evaluate whether pulmonary fibrosis occurs in type 2 diabetes rat models and whether VD3 can prevent it by inhibiting pyroptosis."1.91Vitamin D3 alleviates lung fibrosis of type 2 diabetic rats via SIRT3 mediated suppression of pyroptosis. ( Chen, H; Li, M; Li, W; Li, X; Peng, Y; Song, H; Tang, L; Zhang, D; Zhang, Y, 2023)
"Metformin is a widely used drug for treating type 2 diabetes and is also used for delaying sexual maturation in girls with precocious puberty."1.72Metformin treatment of juvenile mice alters aging-related developmental and metabolic phenotypes. ( Bartke, A; Fang, Y; Medina, D; Yuan, R; Zhu, Y, 2022)
"Weight loss was 0."1.72A Health Care Professional Delivered Low Carbohydrate Diet Program Reduces Body Weight, Haemoglobin A1c, Diabetes Medication Use and Cardiovascular Risk Markers-A Single-Arm Intervention Analysis. ( Brinkworth, GD; Taylor, PJ; Thompson, CH; Wycherley, TP, 2022)
"Non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH) are serious health concerns for which lifestyle interventions are the only effective first-line treatment."1.72Combining Dietary Intervention with Metformin Treatment Enhances Non-Alcoholic Steatohepatitis Remission in Mice Fed a High-Fat High-Sucrose Diet. ( Amigó, N; Baiges-Gaya, G; Camps, J; Castañé, H; Jiménez-Franco, A; Joven, J; Rodríguez-Tomàs, E, 2022)
"Metformin was administered intragastrically, and aerobic exercise was performed using treadmill with 7-12 m/min, 30-40 min/day, 5 days/week."1.62Morphological and functional characterization of diabetic cardiomyopathy in db/db mice following exercise, metformin alone, or combination treatments. ( Liu, J; Lu, J; Tang, Q; Wang, X; Zhang, L; Zhang, Y, 2021)
"A rat model of PCOS-IR was established using a high-fat diet (49 d) combined with letrozole (1 mg/kg·d, for 28 d)."1.62Effects of total flavonoids from Eucommia ulmoides Oliv. leaves on polycystic ovary syndrome with insulin resistance model rats induced by letrozole combined with a high-fat diet. ( Li, CX; Li, M; Miao, MS; Peng, MF; Ren, Z; Song, YG; Tian, S, 2021)
"Metformin is an antidiabetic drug commonly used in obesity treatment."1.56Effect of high-fat diet-induced obesity on thyroid gland structure in female rats and the possible ameliorating effect of metformin therapy. ( El-Sayed, SM; Ibrahim, HM, 2020)
"Rats treated with metformin showed a significant improvement in the aforementioned parameters."1.56Combined treatments with metformin and phosphodiesterase inhibitors alleviate nonalcoholic fatty liver disease in high-fat diet fed rats: a comparative study. ( Abdel-Latif, RG; El-Deen, RM; Heeba, GH; Khalifa, MMA, 2020)
"In this study, mice with type 2 diabetes mellitus (T2DM) induced by high-fat diet were used to investigate the antidiabetic effect and mechanism of action of peanut skin extract (PSE)."1.56Peanut skin extract ameliorates the symptoms of type 2 diabetes mellitus in mice by alleviating inflammation and maintaining gut microbiota homeostasis. ( Osada, H; Pan, W; Qi, J; Wu, Q; Xiang, L; Yoshida, M, 2020)
"Metformin treatment of HFD rats reduced fasting insulin and free fatty acid concentrations and lowered body weight and adiposity."1.51Metformin improves vascular and metabolic insulin action in insulin-resistant muscle. ( Attrill, E; Betik, AC; Bradley, EA; Hu, D; Keske, MA; Premilovac, D; Rattigan, S; Richards, SM, 2019)
"Bariatric surgery leads to type 2 diabetes mellitus (T2DM) remission, but recurrence can ensue afterwards."1.51Long-term diabetes outcomes after bariatric surgery-managing medication withdrawl. ( Belo, S; Carvalho, D; Freitas, P; Magalhães, D; Neves, JS; Oliveira, SC; Pedro, J; Souteiro, P; Varela, A, 2019)
"NAFLD is prevalent in patients with type 2 diabetes mellitus (T2DM), yet only preliminary evidence are available on the effect of anti-diabetic agents to NAFLD in T2DM patients."1.51Reply. ( Weng, J, 2019)
"The hepatoprotective effect of Cs on NAFLD may possibly be due to its antioxidant effect."1.51Hepatoprotective effects of Cassia semen ethanol extract on non-alcoholic fatty liver disease in experimental rat. ( Fang, N; Guo, Y; Liu, Y; Meng, Y, 2019)
" The easy and convenient oncedaily dosing should be customized according to patient needs and glycaemic profiles."1.51Expert Opinion: Use of sodium glucose co-transporter type-2 inhibitors in South Asian population -The Pakistan perspective. ( Aamir, AH; Ahmad, I; Ishtiaq, O; Islam, N; Jawa, A; Khan, K; Khan, KM; Mahar, SA; Naseer, N; Qureshi, FM; Raza, SA, 2019)
"Metformin is an anti-hyperglycemic drug widely used for the treatment of insulin resistance and glucose intolerance and is currently considered for preventing large-for-gestational-age (LGA) offspring in pregnant women affected by obesity or diabetes."1.51Maternal Metformin Treatment Improves Developmental and Metabolic Traits of IUGR Fetuses. ( Astiz, S; Encinas, T; Garcia-Contreras, C; Gonzalez-Bulnes, A; Heras-Molina, A; Pesantez-Pacheco, JL; Torres-Rovira, L; Vazquez-Gomez, M, 2019)
"A rodent model of type 2 diabetes (30 mg/kg streptozotocin and high-fat feeding in male Sprague-Dawley rats) was used to assess 12 weeks of co-treatment with a sodium-glucose cotransporter 2 inhibitor (SGLT2i) and exercise (EX; treadmill running) on glycemic control and exercise capacity."1.51The combination of exercise training and sodium-glucose cotransporter-2 inhibition improves glucose tolerance and exercise capacity in a rodent model of type 2 diabetes. ( Beebe, DA; Braun, B; Esler, WP; Gorgoglione, MF; Hamilton, KL; Linden, MA; Miller, BF; Ross, TT, 2019)
"Polycystic ovary syndrome is one of the most common causes of female infertility, affecting 5-10% of the population."1.51Ocimum kilimandscharicum L. restores ovarian functions in letrozole - induced Polycystic Ovary Syndrome (PCOS) in rats: Comparison with metformin. ( AbdelMaksoud, S; El-Bahy, AA; Handoussa, H; Khaled, N; Radwan, R, 2019)
"Metformin treatment decreased the expression of IL-1β and IL-6 in epididymal fat, which was correlated with the abundance of various bacterial genera."1.48Modulation of the gut microbiota by metformin improves metabolic profiles in aged obese mice. ( An, J; Kim, J; Kim, K; Kong, H; Lee, CK; Lee, H; Lee, S; Lee, Y; Song, Y, 2018)
"Men with type 2 diabetes (T2D) and obesity are often characterised by low testosterone (T)."1.48Short-term combined treatment with exenatide and metformin is superior to glimepiride combined metformin in improvement of serum testosterone levels in type 2 diabetic patients with obesity. ( Hao, M; Kuang, HY; Li, BW; Ma, XF; Pan, J; Shao, N; Wu, WH; Yu, XY; Yu, YM; Zhang, HJ, 2018)
"To analyze the efficacy and safety of replacing sitagliptin with canagliflozin in patients with type 2 diabetes (T2D) and poor metabolic control despite treatment with sitagliptin in combination with metformin and/or gliclazide."1.48Efficacy and safety of replacing sitagliptin with canagliflozin in real-world patients with type 2 diabetes uncontrolled with sitagliptin combined with metformin and/or gliclazide: The SITA-CANA Switch Study. ( Garcia de Lucas, MD; Gómez Huelgas, R; Olalla Sierra, J; Pérez Belmonte, LM; Suárez Tembra, M, 2018)
"Data on 25,386 patients with type 2 diabetes, newly treated with a DPP4 inhibitor (2007-2013), were sourced from a United Kingdom general practice database via the Health Improvement Network database."1.43Determinants of Glycemic Response to Add-On Therapy with a Dipeptidyl Peptidase-4 Inhibitor: A Retrospective Cohort Study Using a United Kingdom Primary Care Database. ( Donnelly, R; Idris, I; Mamza, J; Mehta, R, 2016)
"Metformin was treated daily for 14 weeks in a high-fat dieting C57BL/6J mice."1.43Metformin Prevents Fatty Liver and Improves Balance of White/Brown Adipose in an Obesity Mouse Model by Inducing FGF21. ( Byun, JK; Cho, ML; Choi, JY; Jeong, JH; Jhun, JY; Kim, EK; Kim, JK; Lee, SH; Lee, SY, 2016)
" In STZ-induced diabetic rats the long-term administration of metformin normalized reduced PON1 activity assayed toward paraoxon (+42."1.43The paraoxonase 1 (PON1), platelet-activating factor acetylohydrolase (PAF-AH) and dimethylarginine dimethylaminohydrolase (DDAH) activity in the metformin treated normal and diabetic rats. ( Bełtowski, J; Czechowska, G; Jamroz-Wiśniewska, A; Korolczuk, A; Marciniak, S; Wójcicka, G, 2016)
"A significant decrement of hyperinsulinemia, triglyceridemia, serum IL6 and oxidised LDL were observed at the end of the study."1.43Metformin preconditioned adipose derived mesenchymal stem cells is a better option for the reversal of diabetes upon transplantation. ( Bhonde, RR; Shree, N, 2016)
"The recent type 2 diabetes American Diabetes Association/European Association for the Study of Diabetes (ADA/EASD) position statement suggested insulin is the most effective glucose-lowering therapy, especially when glycated haemoglobin (HbA1c) is very high."1.42Is insulin the most effective injectable antihyperglycaemic therapy? ( Buse, JB; Diamant, M; Donsmark, M; Furber, S; Han, J; MacConell, L; Maggs, D; Peters, A; Russell-Jones, D, 2015)
"Metformin (Met), which is an insulin-sensitizer, decreases insulin resistance and fasting insulin levels."1.42Intracerebroventricular metformin decreases body weight but has pro-oxidant effects and decreases survival. ( Brochier, AW; de Assis, AM; de Carvalho, AK; Gnoatto, J; Haas, CB; Hansel, G; Muller, AP; Oses, JP; Portela, LV; Zimmer, ER, 2015)
"Vildagliptin treatment with or without metformin was generally well tolerated."1.42Clinical effectiveness and safety of vildagliptin in >19 000 patients with type 2 diabetes: the GUARD study. ( Abou Jaoude, E; Al-Arouj, M; DiTommaso, S; Fawwad, A; Latif, ZA; Orabi, A; Rosales, R; Shah, P; Vaz, J, 2015)
"Treatment with liraglutide in randomized controlled trials is associated with significant reductions in glycated hemoglobin (HbA1c) and weight loss in type 2 diabetes patients."1.42Correlation between baseline characteristics and clinical outcomes in a large population of diabetes patients treated with liraglutide in a real-world setting in Italy. ( Balzano, S; Bax, G; Bettio, M; Bonsembiante, B; Brun, E; Cardone, C; Confortin, L; D'Ambrosio, M; Da Tos, V; Dal Frà, MG; Dal Pos, M; Ferrari, M; Frison, V; Gallo, A; Lamonica, M; Lapolla, A; Marangoni, A; Marin, N; Masin, M; Mesturino, CA; Panebianco, G; Pianta, A; Piarulli, F; Rocchini, P; Sartore, G; Simioni, N; Simoncini, M; Strazzabosco, M; Tadiotto, F; Zen, F, 2015)
"Type 2 diabetes is a chronic disease that cannot be treated adequately using the known monotherapies, especially when the disease progresses to an advanced stage."1.42Combination therapy with oleanolic acid and metformin as a synergistic treatment for diabetes. ( Abdelkader, D; Chen, Y; Hassan, W; Liu, J; Sun, H; Wang, X, 2015)
"Treatment with liraglutide resulted in mean decreases in hemoglobin A1c (HbA1c) of -1."1.42Add-On Treatment with Liraglutide Improves Glycemic Control in Patients with Type 2 Diabetes on Metformin Therapy. ( Brunetti, A; Capula, C; Chiefari, E; Foti, D; Greco, M; Liguori, R; Oliverio, R; Puccio, L; Pullano, V; Tirinato, D; Vero, A; Vero, R, 2015)
"Treatment of type 2 diabetes with glucagon-like peptide-1 (GLP-1) receptor agonists may be limited by gastrointestinal side effects (GISE) in some patients."1.42The influence of age and metformin treatment status on reported gastrointestinal side effects with liraglutide treatment in type 2 diabetes. ( Blann, AD; Gupta, PS; Ryder, RE; Thong, KY, 2015)
"The metformin treatment of Wistar rats with obesity induced by high-fat diet was carried out for 2 months (daily dose of 200 mg/kg)."1.42[THE EFFECTS OF LONG-TERM METFORMIN TREATMENT ON THE ACTIVITY OF ADENYLYL CYCLASE SYSTEM AND NO-SYNTHASES IN THE BRAIN AND THE MYOCARDIUM OF RATS WITH OBESITY]. ( Bondareva, VM; Derkach, KV; Ignatieva, PA; Kuznetsova, LA; Sharova, TS; Shpakov, AO, 2015)
"To determine how many ambulatory older adults with chronic kidney disease receive medications that are contraindicated or dosed excessively given their level of renal function."1.42Use of Renally Inappropriate Medications in Older Veterans: A National Study. ( Chang, F; Miao, Y; O'Hare, AM; Steinman, MA, 2015)
"Treatment with metformin was associated with a significant weight reduction (P = 0·033), which resulted from a decrease in BF% (P = 0·044) but was not associated with changes in android and gynoid depots."1.40Changes in adiponectin level and fat distribution in patients with type 2 diabetes. ( Dziwura-Ogonowska, J; Iskierska, K; Miazgowski, T; Safranow, K; Widecka, K, 2014)
"Metformin treatment was similarly evaluated and found not to have adverse effects on pancreas."1.40Characterization of the exocrine pancreas in the male Zucker diabetic fatty rat model of type 2 diabetes mellitus following 3 months of treatment with sitagliptin. ( Cunningham, C; Dey, M; Forest, T; Frederick, C; Holder, D; Prahalada, S; Smith, A; Yao, X, 2014)
"Metformin is a widely prescribed drug for the treatment of type 2 diabetes."1.40Metformin impairs mitochondrial function in skeletal muscle of both lean and diabetic rats in a dose-dependent manner. ( Ciapaite, J; Nicolay, K; Prompers, JJ; van den Broek, NM; Wessels, B, 2014)
"Weight gain was associated with a significant increase in all-cause costs of $3400 per year compared with the weight-neutral cohort; however, differences in T2DM-specific costs and discontinuation rates did not reach significance levels."1.40Economic implications of weight change in patients with type 2 diabetes mellitus. ( Bell, K; D'Souza, A; Graham, J; Lamerato, L; Parasuraman, S; Raju, A; Shah, M, 2014)
"Metformin was administered during gestation from E0."1.40Prenatal metformin exposure in a maternal high fat diet mouse model alters the transcriptome and modifies the metabolic responses of the offspring. ( Ailanen, L; Eerola, K; Heinäniemi, M; Koulu, M; Pesonen, U; Ruohonen, ST; Salomäki, H; Vähätalo, LH, 2014)
"Metformin was used as a standard drug."1.39Anti-diabetic effect of Murraya koenigii (L) and Olea europaea (L) leaf extracts on streptozotocin induced diabetic rats. ( Al-Olayan, EM; Almarhoon, ZM; Daghestani, MH; El-Amin, M; Elobeid, MA; Hassan, ZK; Merghani, NM; Omer, SA; Virk, P, 2013)
"Metformin also inhibited the growth of pancreatic cancer xenografts when administered orally (2."1.39Metformin inhibits the growth of human pancreatic cancer xenografts. ( Eibl, G; Kisfalvi, K; Moro, A; Rozengurt, E; Sinnett-Smith, J, 2013)
"Metformin initiation was associated with a lower risk of kidney function decline or death compared to sulfonylureas, which which appeared to be independent of changes in BMI, SBP, and glycated hemoglobin over time."1.39Kidney function decline in metformin versus sulfonylurea initiators: assessment of time-dependent contribution of weight, blood pressure, and glycemic control. ( Greevy, RA; Griffin, MR; Grijalva, CG; Hung, AM; Liu, X; Murff, HJ; Roumie, CL, 2013)
"Metformin has been reported to increase the expression of the glucagon-like peptide-1 (GLP-1) receptor in pancreatic beta cells in a peroxisome proliferator-activated receptor (PPAR)-α-dependent manner."1.39Effect of the combination of metformin and fenofibrate on glucose homeostasis in diabetic Goto-Kakizaki rats. ( Cho, YM; Kang, GH; Oh, TJ; Park, KS; Shin, JY, 2013)
" We conclude that this treatment intensification approach may be useful, efficient, and safe in daily clinical practice for patients with type 2 diabetes."1.39Efficacy and safety of insulin glargine added to a fixed-dose combination of metformin and a dipeptidyl peptidase-4 inhibitor: results of the GOLD observational study. ( Bramlage, P; Pegelow, K; Seufert, J, 2013)
" This open-label, prospective, multicentre, post-marketing surveillance study was conducted to investigate the efficacy and safety of nateglinide in combination with metformin in Chinese patients with type 2 diabetes (T2DM)."1.39Nateglinide in combination with metformin in Chinese patients with type 2 diabetes mellitus: a post-marketing surveillance study. ( Wang, L; Yang, JK, 2013)
"Nonalcoholic fatty liver disease (NAFLD), one of chronic liver diseases, seems to be rising as the obesity epidemic continues."1.38Synthesis and biological evaluation of 5-benzylidenepyrimidine-2,4,6(1H,3H,5H)-trione derivatives for the treatment of obesity-related nonalcoholic fatty liver disease. ( Chen, J; Chen, L; Huang, L; Lai, H; Liang, X; Liu, J; Ma, L; Pei, H; Peng, A; Ran, Y; Sang, Y; Wei, Y; Xiang, M; Xie, C, 2012)
"Metformin treatment improved these alterations."1.38Improvement of metabolic parameters and vascular function by metformin in obese non-diabetic rats. ( Akamine, EH; Carvalho, MH; Filgueira, FP; Fortes, ZB; Hagihara, GN; Lobato, NS; Pariz, JR; Tostes, RC, 2012)
"Both bortezomib and metformin have been proposed as potential therapeutics in TSC."1.38Therapeutic trial of metformin and bortezomib in a mouse model of tuberous sclerosis complex (TSC). ( Auricchio, N; Kwiatkowski, DJ; Malinowska, I; Manning, BD; Shaw, R, 2012)
"Insulin resistance has been shown to be associated with cardiac sympathovagal imbalance, myocardial dysfunction, and cardiac mitochondrial dysfunction."1.38Cardioprotective effects of metformin and vildagliptin in adult rats with insulin resistance induced by a high-fat diet. ( Apaijai, N; Chattipakorn, N; Chattipakorn, SC; Pintana, H, 2012)
"Rosiglitazone treatment reduced insulin resistance and partially restored β-cell mass in animals with reduced β-cell mass at birth."1.37Effect of combining rosiglitazone with either metformin or insulin on β-cell mass and function in an animal model of Type 2 diabetes characterized by reduced β-cell mass at birth. ( Gerstein, HC; Hettinga, BP; Holloway, AC, 2011)
"Approximately 40% of patients with type 2 diabetes may progress to nephropathy and a good metabolic control can prevent the development of diabetic renal injury."1.37Insulin and metformin may prevent renal injury in young type 2 diabetic Goto-Kakizaki rats. ( da Cunha, FX; Louro, TM; Matafome, PN; Nunes, EC; Seiça, RM, 2011)
"non-alcoholic fatty liver disease (NAFLD) and type 2 diabetes are associated with dyslipidaemia, inflammation and oxidative stress."1.37Metformin and atorvastatin combination further protect the liver in type 2 diabetes with hyperlipidaemia. ( Amaral, C; Cipriano, A; Crisóstomo, J; Louro, T; Matafome, P; Monteiro, P; Nunes, E; Rodrigues, L; Seiça, R, 2011)
"Advanced HF (heart failure) is associated with altered substrate metabolism."1.37Effect of metformin therapy on cardiac function and survival in a volume-overload model of heart failure in rats. ( Benada, O; Benes, J; Cervenka, L; Drahota, Z; Houstek, J; Kazdova, L; Kolar, M; Kopecky, J; Kovarova, N; Medrikova, D; Melenovsky, V; Petrak, J; Sedmera, D; Skaroupkova, P; Strnad, H; Vrbacky, M, 2011)
"Treatment with metformin started at the age of 3 months increased mean life span by 14% and maximum life span by 1 month."1.37If started early in life, metformin treatment increases life span and postpones tumors in female SHR mice. ( Anisimov, VN; Berstein, LM; Egormin, PA; Kovalenko, IG; Piskunova, TS; Popovich, IG; Poroshina, TE; Semenchenko, AV; Tyndyk, ML; Yurova, MN; Zabezhinski, MA, 2011)
"05) reduced hyperglycemia, glibenclamide or metformin combined with honey produced significantly much lower blood glucose (8."1.37Glibenclamide or metformin combined with honey improves glycemic control in streptozotocin-induced diabetic rats. ( Erejuwa, OO; Gurtu, S; Salleh, MS; Sirajudeen, KN; Sulaiman, SA; Wahab, MS, 2011)
"Metformin pre-treatment also reduced endothelial cell damage in ferrous chloride induced thrombosis in carotid arteries."1.37Investigation of the potential effects of metformin on atherothrombotic risk factors in hyperlipidemic rats. ( Bhadada, SV; Dhamecha, PS; Ghatak, SB; Panchal, SJ, 2011)
"Metformin was administered i."1.37The effect of metformin on the myocardial tolerance to ischemia-reperfusion injury in the rat model of diabetes mellitus type II. ( Bairamov, A; Galagudza, M; Grineva, E; Kravchuk, E; Vlasov, T, 2011)
"Metformin is an anti-type II diabetes drug that has anti-inflammatory and anti-oxidant properties, can bring about mitochondrial biogenesis and has been shown to attenuate pathology in mouse models of Huntington's disease and multiple sclerosis."1.37Metformin treatment has no beneficial effect in a dose-response survival study in the SOD1(G93A) mouse model of ALS and is harmful in female mice. ( Kaneb, HM; Rahmani-Kondori, N; Sharp, PS; Wells, DJ, 2011)
"Metformin is a first-line drug for the treatment of type 2 diabetes (T2D) and is often prescribed in combination with other drugs to control a patient's blood glucose level and achieve their HbA1c goal."1.36Toxicity and toxicokinetics of metformin in rats. ( Chism, JP; Jordan, HL; Melich, DH; Nold, JB; Polli, JW; Quaile, MP; Rhodes, MC; Smith, GA, 2010)
"Metformin treatment significantly decreased the blood glucose levels from 15."1.36Metformin normalizes type 2 diabetes-induced decrease in cell proliferation and neuroblast differentiation in the rat dentate gyrus. ( Choi, JW; Hwang, IK; Joo, EJ; Kim, IY; Seong, JK; Shin, JH; Won, MH; Yoon, YS, 2010)
"Body weight was significantly reduced in the metformin group compared with control during the middle of the study, despite similar weekly food intake."1.36Metformin supplementation and life span in Fischer-344 rats. ( Allison, DB; Elam, CF; Ingram, DK; Lane, MA; Mattison, JA; Roth, GS; Smith, DL, 2010)
"Metformin treatment also improved hyperleptinemia, whereas pioglitazone was ineffective."1.36Metformin reduces body weight gain and improves glucose intolerance in high-fat diet-fed C57BL/6J mice. ( Hirasawa, Y; Ito, M; Kyuki, K; Matsui, Y; Sugiura, T; Toyoshi, T, 2010)
"We hypothesized that hyperinsulinemia precedes the development of insulin resistance and increased adiposity in these mice with a defective adipoinsular axis."1.36Hyperinsulinemia precedes insulin resistance in mice lacking pancreatic beta-cell leptin signaling. ( Covey, SD; Donald, C; Gray, SL; Jetha, A; Kieffer, TJ, 2010)
"The animal model of type 2 diabetes with hepatic fibrosis was successfully made."1.36[Effect of metformin on the formation of hepatic fibrosis in type 2 diabetic rats]. ( Chen, BN; Du, GH; Qiang, GF; Shi, LL; Xuan, Q; Yang, XY; Zhang, HA; Zhang, L, 2010)
"Obese patients with type 2 diabetes and impaired glucose tolerance are at increased risk of development of cardiovascular diseases."1.35Effects of basal insulin analog and metformin on glycaemia control and weight as risk factors for endothelial dysfunction. ( Ascić-Buturović, B; Kacila, M, 2008)
"Metformin is an efficient curative and preventive treatment for sleep apnea, suggesting that insulin resistance modifies the ventilatory drive independently of obesity."1.34Sleep apnea is induced by a high-fat diet and reversed and prevented by metformin in non-obese rats. ( Delanaud, S; Dewasmes, G; Geloen, A; Libert, JP; Petitjean, M; Ramadan, W; Wiernsperger, N, 2007)
"Pioglitazone treatment restored MCD activity to non-diabetic level and improved the restrained fatty acid metabolism in myocardial and skeletal muscles caused by insulin-resistant diabetic status."1.33Tissue-specific regulation of malonyl-CoA decarboxylase activity in OLETF rats. ( Ahn, CW; Cha, BS; Kim, HJ; Kim, SK; Lee, HC; Lee, YJ; Park, CW; Shim, WS; Zhao, ZS, 2006)
"Metformin treatment resulted in a modest loss of weight."1.33Stability of body weight in type 2 diabetes. ( Chaudhry, ZW; Gannon, MC; Nuttall, FQ, 2006)
"Metformin treatment significantly improved hyperandrogenism, menstrual cyclicity, body weight, and insulin resistance independent of GNAS1 genotype."1.33The CC genotype of the GNAS T393C polymorphism is associated with obesity and insulin resistance in women with polycystic ovary syndrome. ( Frey, UH; Hahn, S; Janssen, OE; Mann, K; Siffert, W; Tan, S, 2006)
"Patients with type 2 diabetes and complete HbA(1c) (A1C) data and treated with metformin or sulfonylurea monotherapy for at least three visits before receiving dual oral therapy were included (n = 644)."1.33Long-term efficacy of metformin therapy in nonobese individuals with type 2 diabetes. ( Constantino, MI; Molyneaux, LM; Ong, CR; Twigg, SM; Yue, DK, 2006)
"Metformin-HCl was administered to 14-day-old broiler chickens at either 300 or 600 mg/kg per day in the drinking water for 10 d while monitoring BW and feed intake."1.32Hypoglycemia and reduced feed intake in broiler chickens treated with metformin. ( Ashwell, CM; McMurtry, JP, 2003)
"Type 2 diabetes can present as diabetic ketoacidosis in obese adolescent subjects."1.32Type 2 diabetes presenting as diabetic ketoacidosis in adolescence. ( Cox, J; Elkeles, RS; Elwig, C; Poulter, C; Valabhji, J; Watson, M, 2003)
"Metformin is an efficacious long-term use drug in poorly controlled type 2 diabetes patients, either in monotherapy or in combination."1.32Long-term efficacy of steady-dose metformin in type 2 diabetes mellitus: a retrospective study. ( Czupryniak, L; Drzewoski, J, 2003)
"Metformin was present in very low or undetectable concentrations in the plasma of four of the infants who were studied."1.31Transfer of metformin into human milk. ( Hackett, LP; Hale, TW; Ilett, KF; Kohan, R; Kristensen, JH, 2002)
"There is no known treatment for fatty liver, a ubiquitous cause of chronic liver disease."1.31Metformin reverses fatty liver disease in obese, leptin-deficient mice. ( Chuckaree, C; Diehl, AM; Kuhajda, F; Lin, HZ; Ronnet, G; Yang, SQ, 2000)
" Eight-week-old male C57BL/Ks (db/db) mice were sorted into control and exercise groups and dosed daily for 4 weeks with vehicle, metformin (150 mg/kg/d), or acarbose (40 mg/kg/d)."1.31Exercise adds to metformin and acarbose efficacy in db/db mice. ( Reed, MJ; Tang, T, 2001)
"There is no established treatment for steatohepatitis in patients who are not alcoholics."1.31Metformin in non-alcoholic steatohepatitis. ( Bianchi, G; Brizi, M; Marchesini, G; Melchionda, N; Tomassetti, S; Zoli, M, 2001)
"Metformin appears to be an effective medication for the treatment of T2DM in children, but did not seem to be a sufficient long-term monotherapy in our protocol, which required euglycemia for insulin withdrawal."1.31Treatment of type 2 diabetes mellitus in children and adolescents. ( Brosnan, PG; Hardin, DS; Zuhri-Yafi, MI, 2002)
"Commonly used drugs for type 2 diabetes are not ideal."1.30Review of management of type 2 diabetes mellitus. ( Greenaway, TM; Peterson, GM; Randall, CT; Vial, JH; Yap, WS, 1998)
"Metformin-treated rats gained significantly less weight."1.29Prevention of hyperglycemia in the Zucker diabetic fatty rat by treatment with metformin or troglitazone. ( Burant, CF; Polonsky, KS; Pugh, W; Sreenan, S; Sturis, J, 1996)
"Metformin treatment did not lead to an increase of the patients body weight."1.29[The effect of metformin on lactate levels in type II diabetes]. ( Cacáková, V; Perusicová, J; Richtrová, A, 1996)
"A total of 40 NIDDM patients were examined (24 females and 16 males) with a mean age of 55."1.29[Comparison of two treatment models in type-II diabetic patients with poor metabolic control: Preformed combination of glibenclamide 2,5 mg + metformin 400 mg or mono-therapy with sulfonylurea at maximal doses? An evaluation at six months]. ( Cavallo, P; D'Argenzio, R; Merante, D; Morelli, A, 1996)
"Metformin markedly reduced also the hyperinsulinemia of the obese animals without altering their plasma glucose or pancreatic insulin content which may reflect an improved insulin sensitivity after metformin treatment."1.28Subchronic treatment with metformin produces anorectic effect and reduces hyperinsulinemia in genetically obese Zucker rats. ( Huupponen, R; Koulu, M; Pesonen, U; Rouru, J, 1992)
"Gliclazide is a suitable oral hypoglycaemic agent for use in the obese diabetic who cannot be controlled by diet alone."1.27A comparison of treatment with metformin and gliclazide in patients with non-insulin-dependent diabetes. ( Frier, BM; Kay, JW; McAlpine, CH; McAlpine, LG; Storer, AM; Waclawski, ER, 1988)
" Side effects were more common with metformin, particularly in the higher dosage and overall control of the diabetes was achieved in the same proportion of patients (33%)."1.26A comparison of phenformin and metformin in the treatment of maturity onset diabetes. ( Cairns, SA; Hartog, M; Marshall, AJ; Shalet, S, 1977)

Research

Studies (680)

TimeframeStudies, this research(%)All Research%
pre-199034 (5.00)18.7374
1990's44 (6.47)18.2507
2000's163 (23.97)29.6817
2010's359 (52.79)24.3611
2020's80 (11.76)2.80

Authors

AuthorsStudies
Manickam, M1
Ramanathan, M1
Jahromi, MA1
Chansouria, JP1
Ray, AB1
Carney, JR1
Krenisky, JM1
Williamson, RT1
Luo, J4
Carlson, TJ1
Hsu, VL1
Moswa, JL1
Inman, WD1
Jolad, SD1
King, SR1
Cooper, R1
Papi Reddy, K1
Singh, AB2
Puri, A1
Srivastava, AK2
Narender, T1
Ma, L2
Xie, C1
Ran, Y1
Liang, X2
Huang, L2
Pei, H1
Chen, J2
Liu, J4
Sang, Y1
Lai, H1
Peng, A1
Xiang, M1
Wei, Y1
Chen, L5
Zhang, JQ1
Li, SM1
Ma, X2
Zhong, G1
Chen, R1
Li, XS1
Zhu, GF1
Zhou, B1
Guo, B1
Wu, HS1
Tang, L2
Li, X7
Xu, Q1
Li, C1
Wang, L3
Jiang, B1
Shi, D2
Xing, C1
Lv, B1
Zhao, H2
Wang, D2
He, B1
Figueiredo, BS1
Ferreira, FBD1
Barbosa, AM1
Dos Santos, C1
Ortsäter, H1
Rafacho, A1
Cui, J1
Song, L1
Wang, R2
Hu, S1
Yang, Z1
Zhang, Z2
Sun, B1
Cui, W1
Lu, J2
Zhang, L6
Wang, X5
Zhang, Y6
Tang, Q2
Zhu, Y2
Fang, Y1
Medina, D1
Bartke, A1
Yuan, R1
Gao, L4
Huang, H1
Zhang, N2
Fu, Y1
Zhu, D3
Bi, Y3
Feng, W2
Abdalla, MA1
Shah, N1
Deshmukh, H1
Sahebkar, A1
Östlundh, L1
Al-Rifai, RH1
Atkin, SL3
Sathyapalan, T1
Cheng, L1
Fu, Q1
Zhou, L2
Fan, Y2
Liu, F2
Zhang, X5
Lin, W1
Wu, X2
Bakhtyukov, AA1
Derkach, KV2
Sorokoumov, VN1
Stepochkina, AM1
Romanova, IV1
Morina, IY1
Zakharova, IO1
Bayunova, LV1
Shpakov, AO2
Green, CJ1
Marjot, T1
Walsby-Tickle, J1
Charlton, C1
Cornfield, T1
Westcott, F1
Pinnick, KE1
Moolla, A1
Hazlehurst, JM1
McCullagh, J1
Tomlinson, JW1
Hodson, L1
Yu, XJ1
Chen, YM1
Liu, XJ2
Bai, XJ1
Liu, KL1
Fu, LY1
Gao, HL1
Sun, TZ1
Shi, XL1
Qi, J2
Li, Y6
Kang, YM1
Ferrannini, E5
Niemoeller, E3
Dex, T1
Servera, S1
Mari, A1
Ding, Y1
Liu, Y3
Qu, Y1
Lin, M1
Dong, F1
Cao, L1
Lin, S1
Kellerer, M1
Kaltoft, MS2
Lawson, J1
Nielsen, LL1
Strojek, K1
Tabak, Ö1
Jacob, S2
Vadher, K1
Patel, H1
Mody, R1
Levine, JA2
Hoog, M1
Cheng, AY1
Pantalone, KM1
Sapin, H1
Huh, Y1
Kim, YS1
Frias, JP4
Choi, J2
Rosenstock, J9
Popescu, L1
Muehlen-Bartmer, I1
Baek, S2
Ghasemian, F1
Esmaeilnezhad, S1
Nirwan, N1
Vohora, D1
Seo, DH1
Suh, YJ1
Cho, Y1
Ahn, SH1
Seo, S1
Hong, S1
Lee, YH2
Choi, YJ1
Lee, E1
Kim, SH1
Dupak, R1
Hrnkova, J1
Simonova, N1
Kovac, J1
Ivanisova, E1
Kalafova, A1
Schneidgenova, M1
Prnova, MS1
Brindza, J1
Tokarova, K1
Capcarova, M1
Brinkworth, GD1
Wycherley, TP1
Taylor, PJ1
Thompson, CH1
Cheng, Z3
Su, B3
Su, X3
Song, W3
Guo, Y5
Liao, L4
Chen, X7
Li, J5
Tan, X6
Xu, F4
Pang, S3
Wang, K3
Ye, J5
Wang, Y4
Sun, J3
Ji, L7
Carter, EW3
Vadari, HS3
Stoll, S3
Rogers, B3
Resnicow, K3
Heisler, M3
Herman, WH3
Kim, HM3
McEwen, LN3
Volpp, KG3
Kullgren, JT3
Baiges-Gaya, G1
Rodríguez-Tomàs, E1
Castañé, H1
Jiménez-Franco, A1
Amigó, N1
Camps, J1
Joven, J1
Peng, Q1
Ouyang, J1
Wang, Q2
Ren, S1
Xie, H1
Wang, C3
Sun, Y2
Liu, H2
Hei, C1
Sun, M1
Chang, Q1
Liu, X3
Li, G4
He, R1
Cai, H1
Chen, Q3
Duan, Y1
Zhao, Y3
Kamble, P1
Desai, S1
Bhonde, R1
Sanap, A1
Shimpi, J1
Kumbhar, R1
Kokani, M1
Kharat, A1
Aroda, VR3
Nguyên-Pascal, ML1
Denkel, K1
Espinasse, M1
Guo, H1
Lingvay, I1
Zhang, SY1
Bruce, K1
Danaei, Z1
Li, RJW1
Barros, DR1
Kuah, R1
Lim, YM1
Mariani, LH1
Cherney, DZ1
Chiu, JFM1
Reich, HN1
Lam, TKT1
Liu, Z1
Zhang, K1
Zhang, J2
Wang, F2
Zhou, Y1
Wang, M2
Zhou, S1
Li, M8
Wang, S2
Patel, T1
Nageeta, F1
Sohail, R1
Butt, TS1
Ganesan, S1
Madhurita, F1
Ahmed, M1
Zafar, M1
Zafar, W1
Zaman, MU1
Varrassi, G1
Khatri, M1
Kumar, S1
Zhang, D1
Peng, Y2
Song, H1
Chen, H6
Li, W2
Zakaraia, HG1
Salem, HF1
Mostafa, MAA1
Ali, AM1
Rabea, H1
Xie, Z1
Hu, J2
Gu, H1
Małecki, MT1
Batterham, RL1
Sattar, N5
Rodríguez, Á2
Bergman, BK1
Wang, H3
Ghimpeteanu, G1
Lee, CJ1
Ajiboye, BO1
Dada, S1
Fatoba, HO1
Lawal, OE1
Oyeniran, OH1
Adetuyi, OY1
Olatunde, A1
Taher, M1
Khotib, J1
Susanti, D1
Oyinloye, BE1
Bradley, EA1
Premilovac, D1
Betik, AC1
Hu, D1
Attrill, E1
Richards, SM1
Rattigan, S1
Keske, MA1
Chen, W1
Li, P2
Wang, G1
Chen, Y5
Wang, B4
Chen, M3
Lipscombe, LL1
El-Sayed, SM1
Ibrahim, HM1
Zinman, B3
Buse, JB3
Cariou, B2
Harris, SB1
Hoff, ST1
Pedersen, KB1
Tarp-Johansen, MJ1
Araki, E1
Zhang, W1
Xu, JH1
Yu, T1
Chen, QK1
Walton, RG1
Dungan, CM1
Long, DE1
Tuggle, SC1
Kosmac, K1
Peck, BD1
Bush, HM1
Villasante Tezanos, AG1
McGwin, G1
Windham, ST1
Ovalle, F1
Bamman, MM1
Kern, PA1
Peterson, CA1
Taneja, V1
Yang, D1
Yan, J2
Weng, J3
Zekarias, K1
Davey, C1
Seaquist, E1
Blazina, I1
Selph, S1
Bassols, J2
Martínez-Calcerrada, JM2
Osiniri, I1
Díaz-Roldán, F2
Xargay-Torrent, S2
Mas-Parés, B2
Dorado-Ceballos, E1
Prats-Puig, A2
Carreras-Badosa, G2
de Zegher, F4
Ibáñez, L4
López-Bermejo, A3
Coll, AP1
Taskar, P1
Rimmington, D1
Patel, S1
Tadross, JA1
Cimino, I1
Yang, M2
Welsh, P2
Virtue, S1
Goldspink, DA1
Miedzybrodzka, EL1
Konopka, AR1
Esponda, RR1
Huang, JT1
Tung, YCL1
Rodriguez-Cuenca, S1
Tomaz, RA1
Harding, HP1
Melvin, A1
Yeo, GSH1
Preiss, D2
Vidal-Puig, A1
Vallier, L1
Nair, KS1
Wareham, NJ1
Ron, D1
Gribble, FM1
Reimann, F1
Savage, DB1
Allan, BB1
O'Rahilly, S1
Cao, G1
Yi, W1
Li, L3
Cao, X1
Vilsbøll, T1
Ekholm, E1
Johnsson, E6
Garcia-Sanchez, R4
Dronamraju, N1
Jabbour, SA3
Lind, M1
Singh, R1
Bansal, Y1
Sodhi, RK1
Singh, DP1
Bishnoi, M1
Kondepudi, KK1
Medhi, B1
Kuhad, A1
Heeba, GH1
El-Deen, RM1
Abdel-Latif, RG1
Khalifa, MMA1
Lawal, SK1
Adeniji, AA1
Sulaiman, SO1
Akajewole, MM1
Buhari, MO1
Osinubi, AA1
Saad, ZA1
Khodeer, DM1
Zaitone, SA1
Ahmed, AAM1
Moustafa, YM1
Harada, N1
Chung, E1
Elmassry, MM1
Kottapalli, P1
Kottapalli, KR1
Kaur, G1
Dufour, JM1
Wright, K1
Ramalingam, L1
Moustaid-Moussa, N1
Hamood, AN1
Shen, CL1
Zhang, S2
Tu, H1
Yao, J1
Le, J1
Jiang, Z2
Zhang, R1
Huo, P1
Lei, X2
Palliyaguru, DL1
Minor, RK1
Mitchell, SJ1
Palacios, HH1
Licata, JJ1
Ward, TM1
Abulwerdi, G1
Elliott, P1
Westphal, C1
Ellis, JL1
Sinclair, DA1
Price, NL1
Bernier, M1
de Cabo, R1
Papaetis, GS1
Filippou, PK1
Constantinidou, KG1
Stylianou, CS1
Shin, Y1
Moon, JH1
Chin, HJ1
Lim, S2
Day, EA1
Ford, RJ1
Smith, BK1
Mohammadi-Shemirani, P1
Morrow, MR1
Gutgesell, RM1
Lu, R1
Raphenya, AR1
Kabiri, M1
McArthur, AG1
McInnes, N1
Hess, S1
Paré, G1
Gerstein, HC2
Steinberg, GR1
Xiang, L1
Wu, Q1
Osada, H1
Yoshida, M1
Pan, W1
Larsen, AH1
Wiggers, H1
Dollerup, OL1
Jespersen, NR1
Hansson, NH1
Frøkiær, J1
Brøsen, K1
Nørrelund, H1
Bøtker, HE1
Møller, N1
Jessen, N1
Zhuang, Y1
Song, J1
Ying, M1
Wang, DD1
Li, ZP1
Shin, AC1
Balasubramanian, P1
Suryadevara, P1
Zyskowski, J1
Herdt, TH1
MohanKumar, SMJ1
MohanKumar, PS1
Li, D2
Zou, H1
Yin, P1
He, J1
Shao, S1
Yang, Y2
Yu, X1
Guo, W1
Tian, W1
Lin, L1
Xu, X1
Previate, C1
Malta, A1
Miranda, RA1
Martins, IP1
Pavanello, A1
de Oliveira, JC1
Prates, KV1
Alves, VS1
Francisco, FA1
Moreira, VM1
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de Moraes, AMP1
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Inzucchi, SE1
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Kamal-Bahl, SJ1
Brown, JB1
Klein, EJ1
Zhang, B1
Mac, SM1
Poon, TH1
Taylor, KL1
Trautmann, ME2
de Fine Olivarius, N1
Andreasen, AH1
Siersma, V1
Richelsen, B1
Pfützner, A1
Schneider, CA1
Forst, T1
Kautzky-Willer, A1
Tura, A1
Winzer, C1
Wagner, OF1
Ludvik, B1
Hanusch-Enserer, U1
Prager, R2
Pacini, G1
Yarat, A1
Yanardağ, R1
Tunali, T1
Sacan, O1
Gursoy, F1
Emekli, N1
Ustuner, A1
Ergenekon, G1
Chadwick, WA1
Roux, S1
van de Venter, M1
Louw, J1
Oelofsen, W1
Filipczak, R1
Le, TD1
Gumprecht, J1
Hahn, S2
Frey, UH1
Siffert, W1
Tan, S2
Janssen, OE2
Ong, CR1
Molyneaux, LM1
Constantino, MI1
Twigg, SM1
Yue, DK1
Kann, PH1
Wascher, T1
Zackova, V1
Moeller, J1
Medding, J1
Szocs, A1
Mokan, M1
Mrevlje, F1
Regulski, M1
Golnik, KC1
Aregawi, D2
Homan, G1
Moran, L1
Karim, A1
Slater, M1
Bradford, D1
Schwartz, L1
Cao, C1
Laurent, A1
Gomez-Caminero, A1
Ohira, M1
Miyashita, Y1
Ebisuno, M1
Saiki, A1
Endo, K1
Koide, N1
Oyama, T1
Murano, T1
Watanabe, H1
Shirai, K1
Schalkwijk, CG2
Smidt, UM2
Bruno, RV1
de Avila, MA1
Neves, FB1
Nardi, AE1
Crespo, CM1
Sobrinho, AT1
Rangel, N1
El Fakih, Y1
Uzcátegui, E1
Galeazzi, T1
Gutiérrez, MA1
Servigna, M1
Dávila, A1
Uzcátegui, M1
Serrano, A1
Beaulieu, S1
Palomba, S1
Falbo, A1
Russo, T1
Manguso, F1
Tolino, A1
Zullo, F1
De Feo, P1
Orio, F1
Girardin, CM1
Schwitzgebel, VM1
Ramadan, W1
Dewasmes, G1
Petitjean, M1
Wiernsperger, N2
Delanaud, S1
Geloen, A1
Libert, JP1
Marcondes, JA1
Yamashita, SA1
Halpern, A1
Golay, A1
Trolle, B1
Flyvbjerg, A1
Kesmodel, U1
Lauszus, FF1
Benson, S1
Dietz, T1
Lahner, H1
Moeller, LC1
Schmidt, M1
Elsenbruch, S1
Kimmig, R1
Isidro, ML1
Penín, MA1
Nemiña, R1
Cordido, F1
Rochotte, E1
Cohen, SE1
Wu, TH1
Liu, HC1
Pani, LN1
Nathan, DM1
Grant, RW1
Cho, LW1
Krentz, AJ1
Burger, J1
Brodows, R1
Roberts, A1
Raz, I1
Wu, M1
Hussain, S1
Kaufman, KD1
Amatruda, JM1
Langdon, RB1
Stein, PP1
Loeys, T1
Engel, SS1
Halperin, F1
Ingelfinger, JR1
McMahon, GT1
Kusaka, I1
Nagasaka, S1
Horie, H1
Ishibashi, S1
Neff, LM1
Aronne, LJ1
Gao, H1
Xiao, W1
Teerlink, T1
Winther, K1
Belsey, J1
Krishnarajah, G1
Elkind-Hirsch, K1
Marrioneaux, O1
Bhushan, M1
Vernor, D1
Bhushan, R1
Desilets, AR1
Dhakal-Karki, S1
Dunican, KC1
Lean, ME1
Borthwick, LJ1
Billingham, MS1
Hall, RA1
Simpson, S1
Junien, JL1
Chomette, G1
Guillaume, M1
Wajcman, H1
Sterne, J1
Muir, A1
Howe-Davies, SA1
Turner, RC1
Zaïbi, MS1
Padieu, P1
Chessebeuf-Padieu, M1
el Baraka, M1
Rapin, JR1
Rouru, J3
Peltonen, J1
Santti, E2
Hänninen, V1
Goodman, AM1
Virtanen, K1
Rouvari, T1
Jhanwar-Uniyal, M1
Hermann, LS5
Scherstén, B1
Bitzén, PO1
Kjellström, T1
Lindgärde, F1
Melander, A1
Verma, S1
Bhanot, S1
McNeill, JH1
Landin, K1
Tengborn, L1
Campbell, IW3
Garcia-Honduvilla, J1
Martin-Alvarez, PJ1
Vara, E1
Calle, JR1
Munguira, ME1
Marañes, JP1
Dorella, M1
Giusto, M1
Campagnolo, M1
Palatini, P1
Rossi, G1
Ceolotto, G1
Felice, M1
Semplicini, A1
Stumvoll, M2
Fritsch, A1
Grant, PJ1
Carlsen, SM1
Rossvoll, O1
Bjerve, KS1
Følling, I1
Kosegawa, I1
Katayama, S1
Kikuchi, C1
Kashiwabara, H1
Negishi, K1
Ishii, J1
Inukai, K1
Oka, Y1
Sreenan, S1
Sturis, J1
Pugh, W1
Burant, CF1
Polonsky, KS1
Perusicová, J1
Cacáková, V1
Richtrová, A1
Féry, F1
Plat, L1
Balasse, EO1
D'Argenzio, R1
Cavallo, P1
Merante, D2
Morelli, A1
Mori, K1
Nakamura, J1
Koh, N1
Sakakibara, F1
Hamada, Y1
Hara, T1
Komori, T1
Nakashima, E1
Naruse, K1
Takeuchi, N1
Hotta, N1
Briscoe, TA1
Anderson, D1
Usifo, OS1
Cooper, GS1
Robinson, AC1
Burke, J1
Robinson, S1
Johnston, DG1
Damsbo, P1
Hother-Nielsen, O1
Reed, MJ2
Meszaros, K1
Entes, LJ1
Claypool, MD1
Pinkett, JG1
Brignetti, D1
Khandwala, A1
Yap, WS1
Peterson, GM1
Vial, JH1
Randall, CT1
Greenaway, TM1
Johansen, K1
Swislocki, AL1
Khuu, Q1
Liao, E1
Wu, E1
Beza, F1
Lopez, J1
Kwan, G1
Noth, RH1
Avilés-Santa, L1
Sinding, J1
Erle, G1
Lovise, S1
Stocchiero, C1
Lora, L1
Coppini, A1
Marchetti, P1
Yu, JG1
Kruszynska, YT1
Mulford, MI1
Olefsky, JM1
Fritsche, A1
Schmülling, RM1
Lin, HZ1
Yang, SQ1
Chuckaree, C1
Kuhajda, F1
Ronnet, G1
Diehl, AM1
Russell, JC1
Ravel, D1
Pégorier, JP1
Delrat, P1
Jochemsen, R1
O'Brien, SF1
Kelly, SE1
Davidge, ST1
Brindley, DN1
Freemark, M1
Bursey, D1
Fontaine, RN1
Subbiah, MT1
Weber, K1
Illig, E1
Streicher, P1
Sieve-Smith, L2
Tracy, TM1
Lang, JE1
McCullough, P1
Song, S1
Andrikopoulos, S1
Filippis, C1
Thorburn, AW1
Khan, D1
Proietto, J1
Lehtovirta, M1
Forsén, B1
Gullström, M1
Häggblom, M1
Eriksson, JG1
Groop, L2
Tang, T1
Brizi, M1
Bianchi, G1
Tomassetti, S1
Zoli, M1
Melchionda, N1
Baysal, B1
Batukan, M1
Batukan, C1
Kobayashi, S1
Phillips, H1
Abbink, EJ1
Pickkers, P1
Jansen van Rosendaal, A1
Lutterman, JA1
Russel, FG1
Smits, P1
Gokcel, A1
Gumurdulu, Y1
Karakose, H1
Melek Ertorer, E1
Tanaci, N1
BascilTutuncu, N1
Guvener, N1
Kalén, J1
Katzman, P1
Lager, I1
Nilsson, A1
Norrhamn, O1
Sartor, G1
Ugander, L1
Fruehwald-Schultes, B1
Oltmanns, KM1
Toschek, B1
Sopke, S1
Kern, W1
Born, J1
Fehm, HL1
Homburg, R1
Kiersztan, A1
Modzelewska, A1
Jarzyna, R1
Jagielska, E1
Bryła, J1
Suzuki, M1
Odaka, H1
Suzuki, N1
Sugiyama, Y1
Ikeda, H1
Zuhri-Yafi, MI1
Brosnan, PG1
Hardin, DS1
Van Gaal, L1
Usadel, KH1
Ball, M1
Whatmough, I1
Guitard, C1
Larsen, J1
Schneider, SH1
Piper, BA1
Henry, D1
Miles, JM1
Leiter, L1
Wadden, T1
Anderson, JW1
Doyle, M1
Foreyt, J1
Aronne, L1
Klein, S1
Fedele, D1
Tiengo, A1
Nosadini, R1
Marchiori, E1
Briani, G1
Garotti, MC1
Muggeo, M1
Sirtori, CR1
Tremoli, E1
Sirtori, M1
Conti, F1
Paoletti, R1
Fowler, LK1
Clarke, BF3
Kemmer, FW1
Berger, M1
Herberg, L1
Gries, FA1
Dieterle, C1
Streda, M1
Cairns, SA1
Shalet, S1
Marshall, AJ1
Hartog, M1
Klein, W1
Herrmann, A1
Hausmann, VL1
Schubotz, R1
Carpentier, J1
Luyckx, AS1
Lefebvre, PJ1
Brun, JM1
Trischitta, V1
Italia, S1
Mazzarino, S1
Buscema, M1
Rabuazzo, AM1
Sangiorgio, L1
Squatrito, S1
Vigneri, R1
Karlsson, JE1
Sjöstrand, A1
Isnard, F1
André, P1
Noury, J1
Nandeuil, A1
Barzilai, N1
Simonson, DC1
Dornan, TL1
Heller, SR1
Peck, GM1
Tattersall, RB1
Josephkutty, S1
Potter, JM1
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Franssila-Kallunki, A1
Ekstrand, A1
Saloranta, C1
Schalin, C1
Eriksson, J1
McAlpine, LG1
McAlpine, CH1
Waclawski, ER1
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Jung, RT1
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Bolli, P1
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Keiser, G1
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Haese, E1
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Siegenthaler, W1

Clinical Trials (168)

Trial Overview

TrialPhaseEnrollmentStudy TypeStart DateStatus
A 26-Week Randomized, Open-label, Active Controlled, Parallel-group, Study Assessing the Efficacy and Safety of the Insulin Glargine/Lixisenatide Fixed Ratio Combination in Adults With Type 2 Diabetes Inadequately Controlled on GLP-1 Receptor Agonist and [NCT02787551]Phase 3514 participants (Actual)Interventional2016-07-06Completed
Effect of Semaglutide Once-weekly Versus Insulin Aspart Three Times Daily, Both as Add on to Metformin and Optimised Insulin Glargine (U100) in Subjects With Type 2 Diabetes A 52-week, Multi-centre, Multinational, Open-label, Active-controlled, Two Armed,[NCT03689374]Phase 32,274 participants (Actual)Interventional2018-10-01Completed
A 56-week, Multicenter, Double-blind, Placebo-controlled, Randomized Study to Evaluate the Efficacy and Safety of Efpeglenatide Once Weekly in Patients With Type 2 Diabetes Mellitus Inadequately Controlled With Diet and Exercise[NCT03353350]Phase 3406 participants (Actual)Interventional2017-12-05Completed
Efficacy and Safety of Oral Semaglutide Versus Placebo in Subjects With Type 2 Diabetes Mellitus Treated With Insulin. A 52-week, Randomised, Double-blind, Placebo-controlled Trial (PIONEER 8 - Insulin add-on)[NCT03021187]Phase 3731 participants (Actual)Interventional2017-02-02Completed
Novel Actions of Metformin to Augment Resistance Training Adaptations in Older Adults[NCT02308228]Early Phase 1109 participants (Actual)Interventional2015-01-14Completed
Preeclampsia Intervention 4 - A Triple Blind Phase III Randomised Controlled Trial Assessing Metformin to Prolong Gestation in Preterm Preeclampsia[NCT06033131]Phase 3294 participants (Anticipated)Interventional2024-01-22Not yet recruiting
Effects of Metformin Treatment on Myocardial Efficiency in Patients With Heart Failure: A Randomized, Double-blind, Placebo-controlled Study[NCT02810132]Phase 236 participants (Actual)Interventional2017-01-20Completed
A Phase III Randomised, Double-blind, Placebo-controlled, Parallel Group, Efficacy and Safety Study of BI 10773 (10 mg, 25 mg) Administered Orally, Once Daily Over 24 Weeks in Patients With Type 2 Diabetes Mellitus With Insufficient Glycaemic Control Desp[NCT01159600]Phase 31,504 participants (Actual)Interventional2010-07-31Completed
A Phase III Double-blind, Extension, Placebo-controlled Parallel Group Safety and Efficacy Trial of BI 10773 (10 and 25mg Once Daily) and Sitagliptin (100mg Once Daily) Given for Minimum 76 Weeks (Incl. 24 Weeks of Preceding Trial) as Monotherapy or With [NCT01289990]Phase 32,705 participants (Actual)Interventional2011-02-28Completed
A Phase IV, Randomized, Double-blind, Placebo-controlled, Parallel-group Trial to Assess the Effect of 12-week Treatment With the Glucagon-like Peptide-1 Receptor Agonist (GLP-1RA) Liraglutide or Dipeptidyl Peptidase-4 Inhibitor (DPP-4i) Sitagliptin on th[NCT01744236]Phase 470 participants (Actual)Interventional2013-04-30Completed
A PHASE 1, RANDOMIZED, DOUBLE-BLIND, SPONSOR-OPEN, PLACEBO-CONTROLLED STUDY TO ASSESS THE SAFETY, TOLERABILITY, PHARMACOKINETICS, AND PHARMACODYNAMICS OF MULTIPLE ESCALATING ORAL DOSES OF PF-06882961 IN ADULT SUBJECTS WITH TYPE 2 DIABETES MELLITUS[NCT03538743]Phase 198 participants (Actual)Interventional2018-06-25Completed
Effect of Dapagliflozin, Metformin and Physical Activity on Glucose Variability, Body Composition and Cardiovascular Risk in Pre-diabetes[NCT02695810]Phase 2120 participants (Actual)Interventional2016-02-24Completed
Effectiveness of the Treatment With Dapagliflozin and Metformin Compared to Metformin Monotherapy for Weight Loss on Diabetic and Prediabetic Patients With Obesity Class III[NCT03968224]Phase 2/Phase 390 participants (Anticipated)Interventional2018-07-07Recruiting
Family Inclusive Childhood Obesity Treatment Designed for Low Income and Hispanic Families[NCT05041855]658 participants (Anticipated)Interventional2021-11-15Recruiting
Type 2 Diabetes Prevention in Community Health Care Settings for at Risk Children and Mothers[NCT03781102]120 participants (Anticipated)Interventional2019-07-01Suspended (stopped due to COVID19)
A Randomized, Double-Blind Trial Comparing the Effect of Dulaglutide 1.5 mg With Placebo on Glycemic Control in Patients With Type 2 Diabetes on Basal Insulin Glargine[NCT02152371]Phase 3300 participants (Actual)Interventional2014-05-31Completed
Assessment of Metformin as Adjuvant Therapy in Patients With Ulcerative Colitis[NCT04750135]Phase 240 participants (Anticipated)Interventional2021-02-07Not yet recruiting
Diazoxide-mediated Insulin Suppression in Hyperinsulinemic Obese Men, Part III[NCT00631033]Phase 251 participants (Actual)Interventional2008-07-31Completed
A Multicenter, Randomized, Double-Blind, Active Controlled, Parallel Group, Phase 3 Trial to Evaluate the Safety and Efficacy of Add-On Therapy With Saxagliptin and Dapagliflozin Added to Metformin Compared to Add-On Therapy With Saxagliptin in Combinatio[NCT01606007]Phase 31,282 participants (Actual)Interventional2012-07-31Completed
Efficacy and Safety of Saxagliptin and Glimepiride in Chinese Patients With Type 2 Diabetes Controlled Inadequately With Metformin Monotherapy (SPECIFY Study) : a 48-week, Multi-center, Randomized, Open-label Trial[NCT02280486]Phase 4388 participants (Actual)Interventional2015-01-31Completed
A Randomized, Blinded, Placebo-Controlled Study To Evaluate The Effect Fixed-Dose Leucine, Metformin, Sildenafil Combinations(NS-0200) Versus Placebo On Hepatic Fat Assessed By MRI In Non Alcoholic Fatty Liver Disease Patients[NCT02546609]Phase 291 participants (Actual)Interventional2015-11-19Completed
Efficacy of Metformin as add-on Therapy in Non-Diabetic Heart Failure Patients[NCT05177588]Phase 470 participants (Actual)Interventional2021-07-21Completed
Dietary Oxysterols and β-Cell Function Among African Americans[NCT05072587]24 participants (Anticipated)Interventional2021-07-01Recruiting
Restoring Insulin Secretion Adult Medication Study[NCT01779362]Phase 3267 participants (Actual)Interventional2013-04-30Completed
A 26 Week Randomised, Multinational, Open Labelled, 2 Armed, Parallel Group, Treat-to-target Once Daily Treatment Trial With Insulin Detemir Versus Insulin Glargine, Both in Combination With Metformin in Subjects With Type 2 Diabetes[NCT00909480]Phase 4457 participants (Actual)Interventional2009-05-31Completed
The Relationship Between Baseline Body Weight and Glycemic Control Following Metformin Extended-Release Tablets (Glucophage XR) Monotherapy in Chinese Patients With Newly Diagnosed Type 2 Diabetes[NCT00778622]Phase 4371 participants (Actual)Interventional2009-11-30Completed
A 24-week International, Randomized, Parallel-group, Double-blind, Placebo-controlled Phase III Study With a 80-week Extension Period to Evaluate the Efficacy and Safety of Dapagliflozin Therapy When Added to the Therapy of Patients With Type 2 Diabetes W[NCT00673231]Phase 31,240 participants (Actual)Interventional2008-04-30Completed
A 52-Week International, Multi-centre, Randomised, Parallel-group, Double-blind, Active-controlled, Phase III Study With a 156-Week Extension Period to Evaluate the Efficacy and Safety of Dapagliflozin in Combination With Metformin Compared With Sulphonyl[NCT00660907]Phase 31,217 participants (Actual)Interventional2008-03-31Completed
Feasibility Study of Metformin Therapy in Autosomal Dominant Polycystic Kidney Disease.[NCT02903511]Phase 256 participants (Actual)Interventional2016-11-30Completed
Phase 2 Study of ITCA 650 in Subjects With Type 2 Diabetes Mellitus[NCT00943917]Phase 2155 participants (Actual)Interventional2009-08-31Completed
[NCT00004992]Phase 33,234 participants (Actual)Interventional1996-07-31Completed
Diabetes Prevention Program Outcomes Study[NCT00038727]Phase 32,779 participants (Actual)Interventional2002-09-30Active, not recruiting
Prevalence of Metabolic Syndrome and Effects of Adjunctive Metformin on Metabolic Profiles in Clozapine-treated Schizophrenic Patients[NCT01300637]60 participants (Anticipated)Interventional2008-11-30Recruiting
SGLT-2 Inhibitor Empagliflozin Effects on Appetite and Weight Regulation: A Randomised Double-blind Placebo-controlled Trial (The SEESAW Study)[NCT02798744]Phase 468 participants (Actual)Interventional2016-12-31Completed
[NCT01245166]Phase 3220 participants (Anticipated)Interventional2010-11-30Recruiting
A Randomised Controlled Trial for People With Established Type 2 Diabetes During Ramadan: Canagliflozin (Invokana™) vs. Standard Dual Therapy Regimen: The 'Can Do Ramadan' Study[NCT02694263]Phase 425 participants (Actual)Interventional2016-07-31Completed
A Randomized, Double-Blind, Placebo and Active-Controlled, 4-Arm, Parallel Group, Multicenter Study to Evaluate the Efficacy, Safety, and Tolerability of Canagliflozin in the Treatment of Subjects With Type 2 Diabetes Mellitus With Inadequate Glycemic Con[NCT01106677]Phase 31,284 participants (Actual)Interventional2010-05-31Completed
Effect of Anti-diabetic Drugs on Glycemic Variability. A Comparison Between Gliclazide MR (Modified Release) and Dapagliflozin on Glycemic Variability Measured by Continuous Glucose Monitoring (CGM) in Patients With Uncontrolled Type 2 Diabetes[NCT02925559]Phase 4135 participants (Actual)Interventional2016-10-31Completed
The Effect of GLP-1 Agonist, SGLT2 Inhibitor and Their Combination on Endothelial Function, Arterial Stiffness and Left Ventricular Deformation in Patients With Type 2 Diabetes With High Cardiovascular Risk[NCT03878706]240 participants (Anticipated)Observational [Patient Registry]2017-11-03Recruiting
A 24-week, Multicentre, Randomised, Double-Blind, Placebo-Controlled, Parallel-Group, International Phase III Study With 24 Week Extension to Evaluate the Safety and Efficacy of Dapagliflozin 10 mg/Day in Patients With Type 2 Diabetes Who Have Inadequate [NCT00984867]Phase 3833 participants (Actual)Interventional2009-10-31Completed
A Multi-center, Randomized, Double-blind Placebo Controlled Study to Evaluate the Efficacy and Safety of 24 Weeks Treatment With Vildagliptin 50 mg Bid as add-on Therapy to Metformin Plus Glimepiride in Patients With Type 2 Diabetes[NCT01233622]Phase 3317 participants (Actual)Interventional2010-10-31Completed
Efficacy and Safety of the Oral Combined Therapy Glimepiride / Vildagliptin / Metformin in Patients With Type 2 Diabetes With Dual Treatment Failure[NCT04841096]Phase 3172 participants (Anticipated)Interventional2023-03-21Recruiting
Young Adults With Early-onset Obesity Treated With Semaglutide -The RESETTLE Study[NCT05574439]Phase 4170 participants (Anticipated)Interventional2022-06-01Recruiting
Research of Exenatide for Management of Reproductive and Metabolic Dysfunction in Overweight/Obese PCOS Patients With Impaired Glucose Regulation[NCT03352869]Phase 4183 participants (Actual)Interventional2017-11-28Completed
Short Term Weight Loss With Liraglutide and Metformin Before IVF in Infertile Obese PCOS Patients[NCT03034941]Phase 435 participants (Actual)Interventional2014-04-30Completed
Effectiveness of the Combination Liraglutide and Metformin on Weight Loss, Metabolic - Endocrine Parameters and Pregnancy Rate in Women With Polycystic Ovarian Syndrome, Obesity and Infertility[NCT05952882]Phase 3188 participants (Anticipated)Interventional2023-11-01Not yet recruiting
Semaglutide Improves Metabolic Abnormalities and Fertility in Obese Infertile Women With Polycystic Ovary Syndrome: a Prospective, Randomized, Open, Controlled Study[NCT05702905]Phase 475 participants (Anticipated)Interventional2023-04-30Not yet recruiting
The Effect of Liraglutide on Pregnancy Rates in Obese Women With PCOS Undergoing in Vitro Fertilization: a Pilot Randomized Study[NCT03353948]Phase 430 participants (Actual)Interventional2014-09-01Completed
A Multicenter, Randomized, Double-Blind, Placebo-Controlled Study to Determine the Efficacy and Safety of Alogliptin Plus Metformin, Alogliptin Alone, or Metformin Alone in Subjects With Type 2 Diabetes[NCT01023581]Phase 3784 participants (Actual)Interventional2009-11-30Completed
Effect of Dapagliflozin Administration on Metabolic Syndrome, Insulin Sensitivity, and Insulin Secretion[NCT02113241]Phase 2/Phase 324 participants (Actual)Interventional2014-04-30Completed
A 16-wk, Uni-center, Randomized, Double-blind, Parallel, Phase 3b Trial to Evaluate Efficacy of Saxagliptin + Dapagliflozin vs.Dapagliflozin With Regard to EGP in T2DM With Insufficient Glycemic Control on Metformin+/-Sulfonylurea Therapy[NCT02613897]56 participants (Actual)Interventional2016-01-31Completed
Effect of Saxagliptin in Addition to Dapagliflozin and Metformin on Insulin Resistance, Islet Cell Dysfunction, and Metabolic Control in Subjects With Type 2 Diabetes Mellitus on Previous Metformin Treatment[NCT02304081]Phase 464 participants (Actual)Interventional2015-01-31Completed
Effect of Dulaglutide on Liver Fat in Patients With Type 2 Diabetes and Nonalcoholic Fatty Liver Disease: A Randomized Controlled Trial[NCT03590626]60 participants (Actual)Interventional2019-01-01Completed
The Impact of LY2189265 Versus Metformin on Glycemic Control in Early Type 2 Diabetes Mellitus (AWARD-3: Assessment of Weekly AdministRation of LY2189265 in Diabetes-3)[NCT01126580]Phase 3807 participants (Actual)Interventional2010-05-31Completed
Exercise Snacks and Glutamine to Improve Glucose Control in Adolescents With Type 1 Diabetes[NCT03199638]14 participants (Actual)Interventional2016-04-01Completed
A Study of the Effects of Dapagliflozin on Ambulatory Aortic Pressure, Arterial Stiffness and Urine Albumin Excretion in Patients With Type 2 Diabetes[NCT02887677]Phase 485 participants (Actual)Interventional2016-10-31Terminated (stopped due to On February 2019 Astra-Zeneca Greece decided to stop the financial support of the study.)
Empagliflozin as a Modulator of Systemic Vascular Resistance and Cardiac Output in Patients With Type 2 Diabetes[NCT03132181]Phase 240 participants (Actual)Interventional2017-04-24Completed
A Randomized Trial Comparing Two Therapies: Basal Insulin/Glargine, Exenatide and Metformin Therapy (BET) or Basal Insulin/Glargine, Bolus Insulin Lispro and Metformin Therapy (BBT) in Subjects With Type 2 Diabetes Who Were Previously Treated by Basal Ins[NCT00960661]Phase 31,036 participants (Actual)Interventional2009-09-30Completed
Is the Stepping-down Approach a Better Option Than Multiple Daily Injections in Patients With Chronic Poorly-controlled Diabetes on Advanced Insulin Therapy?[NCT02846233]22 participants (Actual)Interventional2016-08-31Completed
Variability of Glucose Assessed in a Randomized Trial Comparing the Initiation of A Treatment Approach With Biosimilar Basal Insulin Analog Or a Titratable iGlarLixi combinatioN in Type 2 Diabetes Among South Asian Subjects (VARIATION 2 SA Trial)[NCT03819790]Phase 4119 participants (Actual)Interventional2018-10-02Completed
Physicians Committee for Responsible Medicine, A Randomized, Crossover Trial of the Effect of a Dietary Intervention on Intracellular Lipid, Insulin Sensitivity, and Glycemic Control in Type 2 Diabetes[NCT04088981]60 participants (Anticipated)Interventional2024-07-31Suspended (stopped due to The study was not initiated due to COVID-19 restrictions.)
A 16-week, Multicentre, Randomised, Double-Blind, Placebo-Controlled Phase III Study to Evaluate the Safety and Efficacy of Dapagliflozin 2.5 mg BID, 5 mg BID and 10 mg QD Versus Placebo in Patients With Type 2 Diabetes Who Are Inadequately Controlled on [NCT01217892]Phase 3400 participants (Actual)Interventional2010-11-30Completed
A Randomized, Double-Blind, 3-Arm Parallel-Group, 2-Year (104-Week), Multicenter Study to Evaluate the Efficacy, Safety, and Tolerability of JNJ-28431754 Compared With Glimepiride in the Treatment of Subjects With Type 2 Diabetes Mellitus Not Optimally Co[NCT00968812]Phase 31,452 participants (Actual)Interventional2009-09-30Completed
Liraglutide Effect and Action in Diabetes (LEAD-5): Effect on Glycaemic Control After Once Daily Administration of Liraglutide in Combination With Glimepiride and Metformin Versus Glimepiride and Metformin Combination Therapy, and Versus Insulin Glargine [NCT00331851]Phase 3584 participants (Actual)Interventional2006-05-31Completed
A Multicenter, Randomized, Double-Blind, Placebo-Controlled, Parallel Group, Phase 3 Trial to Evaluate the Safety and Efficacy of Dapagliflozin as Monotherapy in Subjects With Type 2 Diabetes Who Have Inadequate Glycemic Control With Diet and Exercise[NCT00528372]Phase 31,067 participants (Actual)Interventional2007-09-30Completed
A Multicenter, Randomized, Double-Blind, Phase 3 Trial to Evaluate the Efficacy and Safety of Saxagliptin Added to Insulin Monotherapy or to Insulin in Combination With Metformin in Subjects With Type 2 Diabetes Who Have Inadequate Glycemic Control on Ins[NCT00757588]Phase 3455 participants (Actual)Interventional2008-11-30Completed
A 52-Week International, Multi-centre, Randomized, Parallel-group, Double-blind, Active-controlled, Phase III Study With a 52-Week Extension Period to Evaluate the Safety and Efficacy of Saxagliptin in Combination With Metformin Compared With Sulphonylure[NCT00575588]Phase 3891 participants (Actual)Interventional2007-12-31Completed
A Multicenter, Randomized, Double-Blind Active-Controlled, Phase 3 Trial to Evaluate the Efficacy and Safety of Saxagliptin in Combination With Metformin IR as Initial Therapy Compared to Saxagliptin Monotherapy and to Metformin IR Monotherapy in Subjects[NCT00327015]Phase 31,306 participants (Actual)Interventional2006-05-31Completed
A 24-week, Multicentre, Randomised, Double-Blind, Placebo-Controlled, International Phase III Study With a 28-week Extension Period to Evaluate the Safety and Efficacy of Dapagliflozin 10mg Once Daily in Patients With Type 2 Diabetes Who Have Inadequate G[NCT01392677]Phase 3311 participants (Actual)Interventional2011-10-31Completed
Efficacy of Ipragliflozin Compared With Sitagliptin in Uncontrolled Type 2 Diabetes With Sulfonylurea and Metformin[NCT03076112]Phase 3170 participants (Actual)Interventional2017-04-25Completed
Prospective, Parallel Goups Study, Aimed to Evaluating Possible Benefits of the Treatment of New Generation Hypoglycaemic Drugs Compared to Sulphonylureas for the Tratment of Type 2 Diabetes Mellitus[NCT04272359]138 participants (Anticipated)Observational [Patient Registry]2019-05-06Recruiting
A 12-Week, Phase 2, Randomized, Double-Blinded, Placebo-Controlled, Dose-Ranging, Parallel Group Study to Evaluate the Safety, Tolerability and Efficacy Of Once Daily PF-04971729 And Sitagliptin On Glycemic Control And Body Weight In Adult Patients With T[NCT01059825]Phase 2375 participants (Actual)Interventional2010-02-24Completed
FLAT-SUGAR: FLuctuATion Reduction With inSULin and Glp-1 Added togetheR[NCT01524705]Phase 4102 participants (Actual)Interventional2012-08-31Completed
A Prospective, Randomized, Parallel-group, Adaptive Design Phase IIb/III, Multicenter Study, to Assess the Efficacy of Polychemotherapy for Inducing Remission of Newly Diagnosed Type 2 Diabetes.[NCT04271189]Phase 2/Phase 3180 participants (Anticipated)Interventional2020-09-01Active, not recruiting
A Randomised, Double-blind, Placebo-controlled Parallel Group Efficacy and Safety Trial of BI 10773 (10 and 25 mg Administered Orally Once Daily) Over 24 Weeks in Patients With Type 2 Diabetes Mellitus With Insufficient Glycaemic Control Despite a Backgro[NCT01210001]Phase 3499 participants (Actual)Interventional2010-09-30Completed
The Effect of Liraglutide Versus Placebo When Added to Basal Insulin Analogues With or Without Metformin in Subjects With Type 2 Diabetes[NCT01617434]Phase 3451 participants (Actual)Interventional2012-09-30Completed
Metformin Versus Insulin in Gestational Diabetes. A Randomized Controlled Single Center Trial.[NCT01240785]Phase 4221 participants (Actual)Interventional2006-06-30Completed
A Randomized, Double-Blind, Active-Controlled, Multicenter Study to Evaluate the Efficacy, Safety, and Tolerability of Canagliflozin Versus Sitagliptin in the Treatment of Subjects With Type 2 Diabetes Mellitus With Inadequate Glycemic Control on Metformi[NCT01137812]Phase 3756 participants (Actual)Interventional2010-07-31Completed
A Randomized, Double-Blind, Placebo-Controlled, Parallel-Group, Multicenter Study to Evaluate the Efficacy, Safety, and Tolerability of Canagliflozin as Monotherapy in the Treatment of Subjects With Type 2 Diabetes Mellitus Inadequately Controlled With Di[NCT01081834]Phase 3678 participants (Actual)Interventional2010-03-31Completed
A Randomized, Double-Blind, Placebo-Controlled, 3-Arm, Parallel-Group, Multicenter Study to Evaluate the Efficacy, Safety, and Tolerability of Canagliflozin in the Treatment of Subjects With Type 2 Diabetes Mellitus With Inadequate Glycemic Control on Met[NCT01106625]Phase 3469 participants (Actual)Interventional2010-05-31Completed
A Randomized Trial of Metformin as Adjunct Therapy for Overweight Adolescents With Type 1 Diabetes[NCT01881828]Phase 3164 participants (Actual)Interventional2013-09-30Completed
The Effect of Metformin Versus Placebo, Including Three Insulin-Analogue Regimens With Variating Postprandial Glucose Regulation, on CIMT in T2DM Patients - A Randomized, Multicenter Trial[NCT00657943]Phase 4415 participants (Actual)Interventional2008-04-30Completed
A Randomized, Double-Blind, Placebo-Controlled, Parallel-Group, Multicenter Study to Evaluate the Efficacy, Safety, and Tolerability of Canagliflozin Compared With Placebo in the Treatment of Older Subjects With Type 2 Diabetes Mellitus Inadequately Contr[NCT01106651]Phase 3716 participants (Actual)Interventional2010-06-30Completed
The Efficacy and Safety of Liraglutide Compared to Sitagliptin, Both in Combination With Metformin in Chinese Subjects With Type 2 Diabetes.(LIRA-DPP-4 CHINA™)[NCT02008682]Phase 4368 participants (Actual)Interventional2013-12-31Completed
A Double-blind [Sponsor Unblinded], Randomized, Placebo-controlled, Staggered-parallel Study to Investigate the Safety, Tolerability, and Pharmacodynamics of GSK2890457 in Healthy Volunteers and Subjects With Type 2 Diabetes[NCT01725126]Phase 253 participants (Actual)Interventional2013-02-10Completed
Studies to Treat Or Prevent Pediatric Type 2 Diabetes (STOPP-T2D) Treatment Options for Type 2 Diabetes in Adolescents and Youth (TODAY) Clinical Trial[NCT00081328]Phase 3699 participants (Actual)Interventional2004-05-31Completed
Using Closed-Loop Artificial Pancreas Technology to Reduce Glycemic Variability and Subsequently Improve Cardiovascular Health in Type 1 Diabetes[NCT05653518]40 participants (Anticipated)Interventional2023-09-09Recruiting
A Randomized, Open-label, Active-controlled, 3-arm Parallel-group, 26-week Study Comparing the Efficacy and Safety of Lixisenatide to That of Insulin Glulisine Once Daily and Insulin Glulisine Three Times Daily in Patients With Type 2 Diabetes Insufficien[NCT01768559]Phase 3894 participants (Actual)Interventional2013-01-31Completed
A Multicenter, Randomized, Double Blind Study to Compare the Efficacy and Safety of Sitagliptin/Metformin Fixed-Dose Combination (Janumet®) Compared to Glimepiride in Patients With Type 2 Diabetes Mellitus[NCT00993187]Phase 4292 participants (Actual)Interventional2010-05-04Completed
A Randomized, 24-week, Open-label, 2-arm Parallel-group, Multicenter Study Comparing the Efficacy and Safety of Insulin Glargine/Lixisenatide Fixed Ratio Combination Versus Insulin Glargine on Top of Metformin in Type 2 Diabetic Patients[NCT01476475]Phase 2323 participants (Actual)Interventional2011-11-30Completed
Efficacy and Safety of Liraglutide Versus Lixisenatide as add-on to Metformin in Subjects With Type 2 Diabetes[NCT01973231]Phase 4404 participants (Actual)Interventional2013-10-31Completed
Efficacy and Safety of Switching From Sitagliptin to Liraglutide in Subjects With Type 2 Diabetes Not Achieving Adequate Glycaemic Control on Sitagliptin and Metformin[NCT01907854]Phase 4407 participants (Actual)Interventional2013-12-02Completed
Phase II Study of Metformin for Reduction of Obesity-Associated Breast Cancer Risk[NCT02028221]Phase 2151 participants (Actual)Interventional2014-03-07Completed
Investigation of Pharmacodynamic and Pharmacokinetic Interactions Between 25 mg BI 10773 and 25 mg Hydrochlorothiazide or 5 mg Torasemide Under Steady State Conditions in Patients With Type 2 Diabetes Mellitus in an Open-label, Randomised, Cross-over Tria[NCT01276288]Phase 123 participants (Actual)Interventional2011-01-31Completed
Open-label, Flexible-dose Adjunctive Bromocriptine for Patients With Schizophrenia and Impaired Glucose Tolerance[NCT03575000]Phase 420 participants (Anticipated)Interventional2023-11-01Not yet recruiting
Treatment of Metabolic Abnormalities in Patients With Schizophrenia: Adjunctive Low-dose Metformin in Patients With Schizophrenia and Metabolic Abnormalities[NCT02751307]Phase 455 participants (Actual)Interventional2013-05-31Completed
[NCT02909933]Phase 430 participants (Actual)Interventional2015-07-31Completed
Phase II Randomized Study of Neoadjuvant Metformin Plus Letrozole vs Placebo Plus Letrozole for ER-positive Postmenopausal Breast Cancer[NCT01589367]Phase 2208 participants (Actual)Interventional2012-05-31Completed
Metformin Therapy for Overweight Adolescents With Type 1 Diabetes (T1D)--Insulin Clamp Ancillary Study for Assessment of Insulin Resistance[NCT02045290]Phase 337 participants (Actual)Interventional2014-01-31Completed
Effect of Metformin On Glycaemic Control and Non-Glycaemic Cardiovascular Risk-Factors in Patients With Type-1 Diabetes, With Long-Standing Inadequate Glycaemic Control by Insulin and Diet[NCT00118937]Phase 4100 participants (Actual)Interventional2003-12-31Completed
The Cardiovascular Risk Profile Associated With The Polycystic Ovary Syndrome And With Ovulatory Hyperandrogenism, And Its Changes During Treatment With Metformin Or Oral Contraceptives[NCT00428311]Phase 450 participants Interventional2004-04-30Completed
A Long Term, Open Label, Randomised Study in Patients With Type 2 Diabetes, Comparing the Combination of Rosiglitazone and Either Metformin or Sulfonylurea With Metformin Plus Sulfonylurea on Cardiovascular Endpoints and Glycaemia[NCT00379769]Phase 34,447 participants (Actual)Interventional2001-04-30Completed
Use of Metformin in Prevention and Treatment of Cardiac Fibrosis in PAI-1 Deficient Population[NCT05317806]Phase 415 participants (Anticipated)Interventional2022-10-10Active, not recruiting
Evolution of Abdominal Adipose Tissue Distribution in Type 2 Diabetic Patients Treated During 6 Months With Pioglitazone or Insulin, in Association With Metformin or Sulfonylurea.[NCT00159211]28 participants (Actual)Interventional2005-05-31Terminated (stopped due to inclusion was finished)
A Phase III, Randomized, Parallel, Double-blind, and Non-inferiority Clinical Trial to Compare Efficacy and Safety of CinnaGen-liraglutide to Innovator Liraglutide Product (Victoza®) in Patients With Type II Diabetes (T2D)[NCT03421119]Phase 3300 participants (Anticipated)Interventional2019-06-20Not yet recruiting
Does Metformin Improve Pregnancy Outcomes (Incidence of LGA (≥90% Birth Weight Centile) Babies, Onset of Maternal GDM, Hypertension, PET, Macrosomia, Shoulder Dystocia, Admission to SCBU) in Obese Non-diabetic Women?[NCT01273584]Phase 2/Phase 3450 participants (Actual)Interventional2010-10-31Completed
A Phase 3, Open-Label, Parallel Group Study to Evaluate the Efficacy and Safety of Human Insulin Inhalation Powder (HIIP) Compared to Preprandial Injectable Insulin in Insulin-Naive Patients With Type 2 Diabetes Mellitus.[NCT00325364]Phase 3415 participants (Actual)Interventional2006-04-30Completed
Adaptive Study for Efficacy and Safety of Metformin Glycinate for the Treatment of Patients With MS and DM2, Hospitalized With Severe Acute Respiratory Syndrome Secondary to SARS-CoV-2. Randomized, Double-Blind, Phase IIIb.[NCT04626089]Phase 20 participants (Actual)Interventional2021-02-28Withdrawn (stopped due to Administrative decision of the company)
Dipeptidyl Peptidase-4 Inhibition and Narrow-band Ultraviolet-B Light in Psoriasis (DINUP): A Randomised Clinical Trial[NCT02347501]Phase 2118 participants (Actual)Interventional2013-11-30Completed
Dipeptidyl Peptidase-4 Inhibition in Psoriasis Patients With Diabetes (DIP): A Randomized Clinical Trial.[NCT01991197]Phase 220 participants (Actual)Interventional2014-04-30Completed
The Impact of Glucose Lowering Therapies Including Dipeptidyl Peptidase-4 Inhibitor on Circulating Endothelial Progenitor Cells (EPCs) and Its Mobilising Factor Stromal Derived Factor-1α (SDF-1α) in Patients With Type 2 Diabetes[NCT02694575]241 participants (Actual)Observational2015-03-01Completed
A Pilot Study: Metformin as an Inflammatory Modulating Therapy in Older Adults Without Diabetes[NCT03772964]Phase 1/Phase 232 participants (Actual)Interventional2019-01-22Completed
Effects of the PPAR-gamma Agonist Pioglitazone on Renal and Hormonal Responses to Salt in Diabetic and Hypertensive Subjects[NCT01090752]Phase 416 participants (Actual)Interventional2005-10-31Completed
Metformin in the Treatment of Antipsychotic-Induced Weight Gain in Schizophrenia (METS) - Pilot Study[NCT00816907]Phase 4146 participants (Actual)Interventional2009-01-31Completed
A Randomized Trial Comparing Exenatide With Placebo in Subjects With Type 2 Diabetes on Insulin Glargine With or Without Oral Antihyperglycemic Medications[NCT00765817]Phase 3261 participants (Actual)Interventional2008-10-31Completed
Effects of Metformin on Energy Intake, Energy Expenditure, and Body Weight in Overweight Children With Insulin Resistance[NCT00005669]Phase 2100 participants (Actual)Interventional2000-05-31Completed
Exenatide BID Compared With Insulin Glargine to Change Liver Fat Content in Non-alcoholic Fatty-liver Disease Patients With Type 2 Diabetes[NCT02303730]Phase 476 participants (Actual)Interventional2015-03-31Completed
A Phase 3, Randomized, Open Label, Comparator-Controlled, Parallel Group, Multicenter Study to Compare the Effects of Exenatide and Insulin Glargine on Beta Cell Function and Cardiovascular Risk Markers in Subjects With Type 2 Diabetes Treated With Metfor[NCT00097500]Phase 369 participants (Actual)Interventional2004-09-30Completed
Effect of Exenatide Treatment on Hepatic Fat Content and Plasma Adipocytokine Levels in Patients With Type 2 Diabetes Mellitus[NCT01432405]Phase 424 participants (Actual)Interventional2007-06-30Completed
A Multicentre Observational Study to Investigate the Improvement in Glucose FLuctuation of Sufficient Acarbose Therapy on Type 2 Diabetes Patient With High Blood Glucose Fluctuation[NCT03805191]900 participants (Anticipated)Observational2019-01-01Recruiting
Phase 4 Study Evaluation of the Effects of Acarbose Versus Glibenclamide on Mean Amplitude of Glycemic Excursions and Oxidative Stress in Patients With Type 2 Diabetes Insufficiently Controlled by Metformin[NCT00417729]Phase 451 participants (Actual)Interventional2007-01-31Completed
Effects of Dapagliflozin on Hyperlipidemia, Glycemic Control and Insulin Resistance in Type 2 Diabetic Patients (DAPHNIS Study)[NCT02577159]Phase 450 participants (Anticipated)Interventional2015-07-01Active, not recruiting
ORAL ANTIDIABETICS EFFECT ON VISCERAL FAT MEASURED BY BIOIMPEDANCE IN TYPE 2 DIABETES PATIENTS. Pilot Study.[NCT05032001]30 participants (Anticipated)Interventional2021-08-01Enrolling by invitation
Effect of the Combination of Dipeptidyl Peptidase-4 Inhibitor (DPP4i) and Insulin in Comparison to Insulin on Metabolic Control and Prognosis in Hospitalized Patients With COVID-19[NCT04542213]Phase 370 participants (Actual)Interventional2020-08-01Completed
DPP-4 Inhibitors in Patients With Type 2 Diabetes and Acute Myocardial Infarction:Effects on Platelet Function[NCT02377388]Phase 374 participants (Actual)Interventional2017-02-07Completed
A Multicenter, Randomized, Double-Blind, Active Controlled, Parallel Group, Phase 3 Trial to Evaluate the Safety and Efficacy of Dapagliflozin in Combination With Metformin as Initial Therapy as Compared With Dapagliflozin Monotherapy and Metformin Monoth[NCT00643851]Phase 3994 participants (Actual)Interventional2008-06-30Completed
An Open-Label Study to Examine the Long-Term Effect on Glucose Control (HbA1c) and Safety of AC2993 Given Two Times a Day to Subjects With Type 2 Diabetes Treated With Metformin, a Sulfonylurea, or Metformin and Sulfonylurea Combination[NCT00044668]Phase 3155 participants (Actual)Interventional2002-08-31Completed
Superiority Study of Insulin Glargine Over Sitagliptin in Insulin-naïve Patients With Type 2 Diabetes Treated With Metformin and Not Adequately Controlled[NCT00751114]Phase 4515 participants (Actual)Interventional2008-11-30Completed
The Effect of Liraglutide Compared to Sitagliptin, Both in Combination With Metformin in Subjects With Type 2 Diabetes. A 26-week, Randomised, Open-label, Active Comparator, Three-armed, Parallel-group, Multi-centre, Multinational Trial With a 52-week Ext[NCT00700817]Phase 3665 participants (Actual)Interventional2008-06-30Completed
Effect of Empagliflozin on Liver Fat Content in Patients With Type 2 Diabetes: A 12-week Randomized Clinical Study[NCT02686476]100 participants (Actual)Interventional2016-03-31Completed
Effect of Dapagliflozin vs Sitagliptin on Liver Fat Accumulation and Body Composition in Patients With Diabetes Mellitus and Liver Transplantation: a Randomized Controlled Trial[NCT05042505]100 participants (Anticipated)Interventional2022-01-01Recruiting
Gastric Tolerability and Pharmacokinetics of an Extended Release Metformin and an Immediate Release Metformin[NCT00941239]Phase 124 participants (Actual)Interventional2007-01-31Completed
Double-blind, Randomized Clinical Trial to Evaluate Effect of Combination Therapy of Metformin and Sibutramine Versus Metformin or Sibutramine Monotherapy Over Weight, Adiposity, Glucose Metabolism and Inflammatory State in Obese Patients[NCT00941382]Phase 360 participants (Anticipated)Interventional2008-11-30Active, not recruiting
Clinical Metabolic and Endocrine Parameters in Response to Metformin and Lifestyle Intervention in Women With Polycystic Ovary Syndrome: A Phase 4 Randomized, Double- Blind and Placebo Control Trial[NCT00679679]Phase 430 participants (Actual)Interventional2003-01-31Completed
Effect of Metformin on Healthy Live Birth After In-vitro Fertilization in Women With Prediabetes Mellitus: a Multicenter Double-blind Placebo Controlled Randomized Trial[NCT06064669]988 participants (Anticipated)Interventional2023-10-01Not yet recruiting
Biphasic Insulin Aspart 70/30 + Metformin Compared to Insulin Glargine + Metformin in Type 2 Diabetes Failing OAD Therapy[NCT00598793]Phase 3242 participants (Actual)Interventional2002-11-30Completed
Modulation of Insulin Secretion and Insulin Sensitivity in Bangladeshi Type 2 Diabetic Subjects by an Insulin Sensitizer Pioglitazone and T2DM Association With PPARG Gene Polymorphism.[NCT01589445]Phase 477 participants (Actual)Interventional2008-11-30Completed
A Phase 3, Randomized, Triple-Blind, Parallel-Group, Long-Term, Placebo-Controlled, Multicenter Study to Examine the Effect on Glucose Control (HbA1c) of AC2993 Given Twice Daily in Subjects With Type 2 Diabetes Mellitus Treated With Metformin and a Sulfo[NCT00035984]Phase 3734 participants (Actual)Interventional2002-05-31Completed
A Phase 3, Randomized, Triple-Blind, Parallel-Group, Long-Term, Placebo-Controlled, Multicenter Study to Examine the Effect on Glucose Control (HbA1c) of AC2993 Given Two Times a Day in Subjects With Type 2 Diabetes Mellitus Treated With Metformin Alone[NCT00039013]Phase 3336 participants (Actual)Interventional2002-03-31Completed
Observational Study of Interstitial Glucose Monitoring With Continuous Glucose Monitoring to Track Patients Treated With Exenatide[NCT00569907]18 participants (Actual)Observational2007-01-31Completed
Phase IV Study of Ramelteon as an Adjunct Therapy in Non-Diabetic Patients With Schizophrenia[NCT00595504]Phase 425 participants (Actual)Interventional2008-01-31Completed
Phase 4 Study of the Effects of Pravastatin on Cholesterol Levels, Inflammation and Cognition in Schizophrenia[NCT01082588]Phase 460 participants (Actual)Interventional2010-06-30Completed
Basal Insulin Therapy in Patients With Insulin Resistance: A 6 Month Comparison of Insulin Glargine and NPH Insulin[NCT01854723]Phase 40 participants (Actual)Interventional2013-04-30Withdrawn
Comparison of Carbohydrate Metabolism During the Night and at Hypoglycemia in Type-2 Diabetic Patients Either on Glargine or NPH Insulin[NCT00468364]12 participants (Actual)Observational2003-07-31Completed
Bedtime Insulin Glargine or Bedtime Neutral Protamine Lispro Combined With Sulfonylurea and Metformin in Type 2 Diabetes. A Randomized, Controlled Trial[NCT00641407]Phase 4100 participants (Actual)Interventional2007-01-31Completed
An Open Label Study to Examine the Long Term Effect on Glucose Control (HbA1c) and Safety and Tolerability of Exenatide Given Two Times a Day to Subjects With Type 2 Diabetes Mellitus[NCT00111540]Phase 3456 participants (Actual)Interventional2002-11-30Completed
Magnetic Resonance Assessment of Victoza Efficacy in the Regression of Cardiovascular Dysfunction In Type 2 Diabetes Mellitus[NCT01761318]Phase 450 participants (Actual)Interventional2013-11-30Completed
Effect on Glycemic Control of Individual Maximum Effective Dose of NNC 90-1170 as Add on Therapy to Metformin Compared to Monotherapy of NNC 90-1170 or Metformin or a Metformin-SU Combination Therapy in Patients With Type 2 Diabetes. A Double-blind, Doubl[NCT01511172]Phase 2145 participants (Actual)Interventional2002-08-31Completed
Comparison of Efficacy and Safety of Biphasic Insulin Aspart 30 Plus Metformin With Insulin Glargine Plus Glimepiride in Type 2 Diabetes[NCT00619697]Phase 4260 participants (Actual)Interventional2003-12-31Completed
Descriptive, Transversal Study of Evaluation of Cardiovascular Risks Factors and Prevalence of Metabolic Syndrome in the Different Phenotypes of Women With Polycystic Ovary Syndrome[NCT00784615]80 participants (Anticipated)Observational2007-12-31Recruiting
Randomized, Cross-over Trial With Metformin in Women With Polycystic Ovary Syndrome[NCT02280057]Phase 456 participants (Actual)Interventional2001-09-30Completed
Vildagliptin Compared to Pioglitazone in Combination With Metformin in Patients With Type 2 Diabetes[NCT00237237]Phase 3588 participants Interventional2005-10-31Completed
Effects of Sitagliptin on Postprandial Glycaemia, Incretin Hormones and Blood Pressure in Type 2 Diabetes - Relationship to Gastric Emptying[NCT02324010]Phase 214 participants (Actual)Interventional2015-07-31Completed
Efficacy and Safety of Add-on Topiramate vs Metformin on Cardio-Metabolic Profile in Patients With Schizophrenia on Atypical Antipsychotics With Metabolic Syndrome: a Randomized Controlled Trial[NCT05663749]Phase 460 participants (Actual)Interventional2022-09-20Completed
A Multicenter, Double-Blind, Randomized Study to Evaluate the Safety and Efficacy of the Addition of Sitagliptin to Patients With Type 2 Diabetes Mellitus Who Have Inadequate Glycemic Control on Metformin Therapy[NCT00337610]Phase 3190 participants (Actual)Interventional2006-06-30Completed
Efficacy, Safety & Tolerability of Combination of Ertugliflozin and Sitagliptin in Patients With Type II Diabetes Mellitus[NCT05556291]190 participants (Anticipated)Observational2022-12-01Recruiting
[NCT00684528]Phase 31,000 participants (Anticipated)Interventional2008-06-30Recruiting
A Multicenter, Double-Blind, Placebo and Active Controlled, Randomized Study to Evaluate the Safety and Efficacy of the Addition of Sitagliptin 100 mg Once Daily in Patients With Type 2 Diabetes With Inadequate Glycemic Control on Metformin Monotherapy[NCT00541775]Phase 3273 participants (Actual)Interventional2006-06-30Completed
Effects of Triple Drug Cocktail Therapy on Metabolic, Endocrine Alterations and Perceived Stress Response in Patients With PCOS: A Double Blind Randomized Clinical Trial[NCT04113889]Phase 2147 participants (Actual)Interventional2019-10-15Completed
Comparison of the Effects of Monotherapy With Exenatide or Metformin to Combined Exenatide and Metformin Therapy on Menstrual Cyclicity in Overweight Women With Polycystic Ovary Syndrome[NCT00344851]Phase 260 participants (Actual)Interventional2006-06-30Completed
Metformin Pharmacology in Human Cancers[NCT03477162]Early Phase 118 participants (Actual)Interventional2018-05-15Terminated (stopped due to Enrollment was closed as efforts had become more challenging, and the lab indicated that they were able to obtain their primary objective with the number that had already been enrolled.)
A Randomized Phase 3 Trial of Metformin in Patients Initiating Androgen Deprivation Therapy as Prevention and Intervention of Metabolic Syndrome: The Prime Study[NCT03031821]Phase 3168 participants (Actual)Interventional2018-07-12Terminated (stopped due to Manufacturer discontinued the production of study drugs.)
A Randomized, Placebo-controlled, Double-blind Multicenter Phase II Study to Investigate the Protectivity and Efficacy of Metformin Against Steatosis in Combination With FOLFIRI and Cetuximab in Subjects With First-line Palliative Treated, KRAS-Wild-Type,[NCT01523639]Phase 28 participants (Actual)Interventional2012-04-30Terminated (stopped due to Prematurely due to slow recruitment (07/08/2013). Newly defined study end=LPLV=05/11/2013. ABCSG guaranteed completed treatment period for ethical reasons.)
Double-blind Randomized Trial Using Oral Metformin Versus Placebo in the Treatment of Acanthosis Nigricans in Children With Obesity[NCT02438020]Phase 430 participants (Anticipated)Interventional2015-06-30Not yet recruiting
Randomized Clinical Trial, Effect of Metformin and Rosiglitazone Over Glucose Homeoastasis in no Diabetic With Metabolic Syndrome Patients.[NCT04148183]Phase 2/Phase 330 participants (Actual)Interventional2004-01-01Completed
Fish Oil and Diet for the Treatment of Non-Alcoholic Steatohepatitis (NASH)[NCT00845845]Phase 212 participants (Actual)Interventional2006-03-31Terminated (stopped due to Terminated due to low enrollment.)
Effects of Metformin on Fertility and Pregnancy in Women With Polycystic Ovary Syndrome: a Randomized, Prospective, Placebo-controlled Multicenter Study[NCT00994812]Phase 3326 participants (Actual)Interventional2002-08-31Completed
Open-Label Study Of Metformin In Combination With Simvastatin For Men With Prostate Carcinoma And A Rising Serum Prostate-Specific Antigen Level After Radical Prostatectomy And/Or Radiation Therapy[NCT01561482]Phase 20 participants (Actual)Interventional2012-01-31Withdrawn (stopped due to Study closed due to slow/low enrollment; no subjects were enrolled.)
[information is prepared from clinicaltrials.gov, extracted Sep-2024]

Trial Outcomes

Change From Baseline in 2-Hour Blood Glucose Excursion During Standardized Meal Test to Week 26: Core Period

2-hour plasma glucose excursion = 2-hour PPG value minus plasma glucose value obtained 30 minutes prior to the start of meal and before investigational medicinal product (IMP) administration if IMP was injected before breakfast. Change in plasma glucose excursions were calculated by subtracting baseline value from Week 26 value. Missing data was imputed using LOCF. (NCT02787551)
Timeframe: Baseline, Week 26

Interventionmmol/L (Least Squares Mean)
Insulin Glargine/Lixisenatide Fixed Ratio Combination (FRC)-1.51
GLP-1 Receptor Agonist-0.52

Change From Baseline in 2-Hour Blood Glucose Excursion During Standardized Meal Test to Week 52: Single Arm Extension Period

2-hour plasma glucose excursion = 2-hour PPG value minus plasma glucose value obtained 30 minutes prior to the start of meal and before IMP administration if IMP was injected before breakfast. Change in plasma glucose excursions were calculated by subtracting baseline value from Week 52 value. Missing data was imputed using LOCF. (NCT02787551)
Timeframe: Baseline, Week 52

Interventionmmol/L (Mean)
Insulin Glargine/Lixisenatide Fixed Ratio Combination (FRC)-1.85

Change From Baseline in 2-Hour Postprandial Plasma Glucose (PPG) During Standardized Meal Test to Week 26: Core Period

The 2-hour PPG test measured blood glucose 2 hours after eating a liquid standardized breakfast meal. Change in PPG was calculated by subtracting baseline value from Week 26 value. Missing data was imputed using last observation carried forward (LOCF). (NCT02787551)
Timeframe: Baseline, Week 26

Interventionmmol/L (Least Squares Mean)
Insulin Glargine/Lixisenatide Fixed Ratio Combination (FRC)-3.96
GLP-1 Receptor Agonist-1.11

Change From Baseline in 2-Hour Postprandial Plasma Glucose (PPG) During Standardized Meal Test to Week 52: Single Arm Extension Period

The 2-hour PPG test measured blood glucose 2 hours after eating a liquid standardized breakfast meal. Change in PPG was calculated by subtracting baseline value from Week 52 value. Missing data was imputed using LOCF. (NCT02787551)
Timeframe: Baseline, Week 52

Interventionmmol/L (Mean)
Insulin Glargine/Lixisenatide Fixed Ratio Combination (FRC)-4.30

Change From Baseline in Body Weight at Week 26: Core Period

Change in body weight was calculated by subtracting baseline value from Week 26 value. (NCT02787551)
Timeframe: Baseline, Week 26

Interventionkilogram (kg) (Least Squares Mean)
Insulin Glargine/Lixisenatide Fixed Ratio Combination (FRC)1.89
GLP-1 Receptor Agonist-1.14

Change From Baseline in Body Weight to Week 52: Single Arm Extension Period

Change in body weight was calculated by subtracting baseline value from Week 52 value. (NCT02787551)
Timeframe: Baseline, Week 52

Interventionkg (Mean)
Insulin Glargine/Lixisenatide Fixed Ratio Combination (FRC)2.78

Change From Baseline in Fasting Plasma Glucose (FPG) to Week 26: Core Period

Change in FPG was calculated by subtracting baseline value from Week 26 value. Adjusted LS means and SE were obtained from MMRM to account for missing data using all available post baseline data during the 26 week treatment period. (NCT02787551)
Timeframe: Baseline, Week 26

Interventionmillimoles per litre (mmol/L) (Least Squares Mean)
Insulin Glargine/Lixisenatide Fixed Ratio Combination (FRC)-2.28
GLP-1 Receptor Agonist-0.60

Change From Baseline in Fasting Plasma Glucose (FPG) to Week 52: Single Arm Extension Period

Change in FPG was calculated by subtracting baseline value from Week 52 value. (NCT02787551)
Timeframe: Baseline, Week 52

Interventionmmol/L (Mean)
Insulin Glargine/Lixisenatide Fixed Ratio Combination (FRC)-2.27

Change From Baseline in Glycated Hemoglobin (HbA1c) to Week 26: Core Period

Change in HbA1c was calculated by subtracting baseline value from Week 26 value. Adjusted least squares (LS) mean and standard error (SE) were obtained from Mixed-effect model with repeated measures (MMRM) to account for missing data using all available post baseline data during the 26 week treatment period. (NCT02787551)
Timeframe: Baseline, Week 26

Interventionpercentage of HbA1c (Least Squares Mean)
Insulin Glargine/Lixisenatide Fixed Ratio Combination (FRC)-1.02
GLP-1 Receptor Agonist-0.38

Change From Baseline in Glycated Hemoglobin (HbA1c) to Week 52: Single Arm Extension Period

Change in HbA1c was calculated by subtracting baseline value from Week 52 value. (NCT02787551)
Timeframe: Baseline, Week 52

Interventionpercentage of HbA1c (Mean)
Insulin Glargine/Lixisenatide Fixed Ratio Combination (FRC)-1.01

Change From Baseline in the Daily Average of the 7-point Self-monitored Plasma Glucose (SMPG) to Week 26: Core Period

The 7-point SMPG profile was measured at the following 7 points: pre-prandial and 2 hours postprandial for breakfast, lunch, dinner and at bedtime. Two hours postprandial (breakfast, lunch and dinner) was defined as 2 hours after the start of the meal. Adjusted LS means and SE were obtained from MMRM to account for missing data using all available post baseline data during the 26 week treatment period. (NCT02787551)
Timeframe: Baseline, Week 26

Interventionmmol/L (Least Squares Mean)
Insulin Glargine/Lixisenatide Fixed Ratio Combination (FRC)-1.69
GLP-1 Receptor Agonist-0.67

Change From Baseline in the Daily Average of the 7-point Self-monitored Plasma Glucose (SMPG) to Week 52: Single Arm Extension Period

The 7-point SMPG profile was measured at the following 7 points: pre-prandial and 2 hours postprandial for breakfast, lunch, dinner and at bedtime. Two hours postprandial (breakfast, lunch and dinner) was defined as 2 hours after the start of the meal. (NCT02787551)
Timeframe: Baseline, Week 52

Interventionmmol/L (Mean)
Insulin Glargine/Lixisenatide Fixed Ratio Combination (FRC)-1.68

Percentage of Participants Requiring Rescue Therapy During the 26 Week Treatment Period: Core Period

Routine HbA1c value was used to determine the requirement of rescue medication. Threshold values at Week 12 or later on Week 12: HbA1c >8%. (NCT02787551)
Timeframe: From Baseline to Week 26

Interventionpercentage of participants (Number)
Insulin Glargine/Lixisenatide Fixed Ratio Combination (FRC)4.8
GLP-1 Receptor Agonist15.0

Percentage of Participants Requiring Rescue Therapy During the 52 Week Treatment Period: Single Arm Extension Period

Routine HbA1c value was used to determine the requirement of rescue medication. Threshold values at Week 12 or later on Week 12: HbA1c >8%. (NCT02787551)
Timeframe: From Week 26 to Week 52

Interventionpercentage of participants (Number)
Insulin Glargine/Lixisenatide Fixed Ratio Combination (FRC)1.5

Number of Documented Symptomatic Hypoglycemia Events Per Participant-Year: Core Period

Documented symptomatic hypoglycemia was an event during which symptoms of hypoglycemia were accompanied by a measured plasma glucose concentration of <=3.9 mmol/L (70 mg/dL). Hypoglycemic episodes with plasma glucose of <3.0 mmol/L (54 mg/dL) were also analyzed. (NCT02787551)
Timeframe: From Baseline to Week 26

,
Interventionevents per participant-year (Number)
Documented symptomatic hypoglycemia(<=3.9 mmol/L)Documented symptomatic hypoglycemia (<3.0 mmol/L)
GLP-1 Receptor Agonist0.080.01
Insulin Glargine/Lixisenatide Fixed Ratio Combination (FRC)1.540.25

Number of Documented Symptomatic Hypoglycemia Events Per Participant-Year: Single Arm Extension Period

Documented symptomatic hypoglycemia was an event during which symptoms of hypoglycemia were accompanied by a measured plasma glucose concentration of <=3.9 mmol/L (70 mg/dL). Hypoglycemic episodes with plasma glucose of <3.0 mmol/L (54 mg/dL) were also analyzed. (NCT02787551)
Timeframe: From Baseline to Week 52

Interventionevents per participant-year (Number)
Documented symptomatic hypoglycemia(<=3.9 mmol/L)Documented symptomatic hypoglycemia (<3.0 mmol/L)
Insulin Glargine/Lixisenatide Fixed Ratio Combination (FRC)1.590.24

Percentage of Participants Reaching HbA1c <7 % or <=6.5% at Week 52: Single Arm Extension Period

Participants without any available HbA1c assessment at Week 52 were considered as non-responders. (NCT02787551)
Timeframe: Week 52

Interventionpercentage of participants (Number)
HbA1c <7%HbA1c <=6.5%
Insulin Glargine/Lixisenatide Fixed Ratio Combination (FRC)64.142.7

Percentage of Participants Reaching HbA1c <7% or <=6.5% at Week 26: Core Period

Participants without any available HbA1c assessment at Week 26 were considered as non-responders. (NCT02787551)
Timeframe: Week 26

,
Interventionpercentage of participants (Number)
HbA1c <7%HbA1c <=6.5%
GLP-1 Receptor Agonist25.79.9
Insulin Glargine/Lixisenatide Fixed Ratio Combination (FRC)61.940.5

Change From Baseline in Glycated Haemoglobin (HbA1c)

Change from baseline in HbA1c at week 52 is presented. Data is reported for 'on-treatment' observation period: from the date of first dose of trial product (week 0) to the last date on trial product with a visit window of +7 days (week 52). (NCT03689374)
Timeframe: Baseline (week 0), week 52

InterventionPercentage of HbA1c (Mean)
Semaglutide-1.5
Insulin Aspart-1.2

Change From Baseline to Week 52 in 7-point Self-measured Plasma Glucose Profile (SMPG ): Mean 7-point Profile (7-PP)

Change from baseline in 7-point self-measured plasma glucose profile: mean 7-PP at week 52 is presented. All participants were instructed to perform 7-point SMPG profiles before breakfast, 90 minutes after the start of breakfast, before lunch, 90 minutes after the start of lunch, before main evening meal (dinner), 90 minutes after the start of main evening meal (dinner) and at bedtime. The measurements were to be performed before any injection of bolus insulin and just before the start of the meal (breakfast, lunch or main evening meal), and values measured before breakfast were performed in a fasting condition. Data is reported for 'on-treatment' observation period: from the date of first dose of trial product (week 0) to the last date on trial product with a visit window of +7 days (week 52). (NCT03689374)
Timeframe: Baseline (week 0), week 52

Interventionmmol/L (Mean)
Semaglutide-2.1
Insulin Aspart-2.1

Change From Baseline to Week 52 in 7-point Self-measured Plasma Glucose Profile: Mean Post-prandial Increment (Over All Meals)

Change from baseline in 7-point SMPG profile: mean post-prandial increment (over all meals) at week 52 is presented. Data is reported for 'on-treatment' observation period: from the date of first dose of trial product (week 0) to the last date on trial product with a visit window of +7 days (week 52). (NCT03689374)
Timeframe: Baseline (week 0), week 52

Interventionmmol/L (Mean)
Semaglutide-0.7
Insulin Aspart-0.9

Change From Baseline to Week 52 in Body Mass Index (BMI)

Change from baseline in BMI at week 52 is presented. Data is reported for 'on-treatment' observation period: from the date of first dose of trial product (week 0) to the last date on trial product with a visit window of +7 days (week 52). (NCT03689374)
Timeframe: Baseline (week 0), week 52

Interventionkilograms per meter square (kg/m^2) (Mean)
Semaglutide-1.5
Insulin Aspart1.0

Change From Baseline to Week 52 in Body Weight (Kilogram (kg))

Change from baseline in body weight at week 52 is presented. Data is reported for 'on-treatment' observation period: from the date of first dose of trial product (week 0) to the last date on trial product with a visit window of +7 days (week 52). (NCT03689374)
Timeframe: Baseline (week 0), week 52

Interventionkilograms (Mean)
Semaglutide-4.2
Insulin Aspart2.9

Change From Baseline to Week 52 in Body Weight (Percentage): Ratio to Baseline

Change from baseline in body weight (measured in percentage) at week 52 is presented as ratio to baseline. Data is reported for 'on-treatment' observation period: from the date of first dose of trial product (week 0) to the last date on trial product with a visit window of +7 days (week 52). (NCT03689374)
Timeframe: Baseline (week 0), week 52

InterventionRatio of body weight (Mean)
Semaglutide1.0
Insulin Aspart1.0

Change From Baseline to Week 52 in Fasting Blood Lipids: High-density Lipoprotein (HDL) Cholesterol (Ratio to Baseline)

Change from baseline in HDL cholesterol (measured in mmol/L) at week 52 is presented as ratio to baseline. Data is reported for 'on-treatment' observation period: from the date of first dose of trial product (week 0) to the last date on trial product with a visit window of +7 days (week 52). (NCT03689374)
Timeframe: Baseline (week 0), week 52

InterventionRatio of HDL cholesterol (Geometric Mean)
Semaglutide1.0
Insulin Aspart1.0

Change From Baseline to Week 52 in Fasting Blood Lipids: Low-density Lipoprotein (LDL) Cholesterol (Ratio to Baseline)

Change from baseline in LDL cholesterol (measured in mmol/L) at week 52 is presented as ratio to baseline. Data is reported for 'on-treatment' observation period: from the date of first dose of trial product (week 0) to the last date on trial product with a visit window of +7 days (week 52). (NCT03689374)
Timeframe: Baseline (week 0), week 52

InterventionRatio of LDL cholesterol (Geometric Mean)
Semaglutide1.0
Insulin Aspart1.0

Change From Baseline to Week 52 in Fasting Blood Lipids: Total Cholesterol (Ratio to Baseline)

Change from baseline in total cholesterol (measured in mmol/L) at week 52 is presented as ratio to baseline. Data is reported for 'on-treatment' observation period: from the date of first dose of trial product (week 0) to the last date on trial product with a visit window of +7 days (week 52). (NCT03689374)
Timeframe: Baseline (week 0), week 52

InterventionRatio of total cholesterol (Geometric Mean)
Semaglutide1.0
Insulin Aspart1.0

Change From Baseline to Week 52 in Fasting Blood Lipids: Triglycerides (Ratio to Baseline)

Change from baseline in triglycerides (measured in mmol/L) at week 52 is presented as ratio to baseline. Data is reported for 'on-treatment' observation period: from the date of first dose of trial product (week 0) to the last date on trial product with a visit window of +7 days (week 52). (NCT03689374)
Timeframe: Baseline (week 0), week 52

InterventionRatio of triglycerides (Geometric Mean)
Semaglutide0.9
Insulin Aspart1.0

Change From Baseline to Week 52 in Fasting Plasma Glucose (FPG)

Change from baseline in FPG at week 52 is presented. Data is reported for 'on-treatment' observation period: from the date of first dose of trial product (week 0) to the last date on trial product with a visit window of +7 days (week 52). (NCT03689374)
Timeframe: Baseline (week 0), week 52

Interventionmillimoles per liter (mmol/L) (Mean)
Semaglutide-1.3
Insulin Aspart-0.8

Change From Baseline to Week 52 in Pulse Rate

Change from baseline in pulse rate at week 52 is presented. Data is reported for 'on-treatment' observation period: from the date of first dose of trial product (week 0) to the last date on trial product with a visit window of +7 days (week 52). (NCT03689374)
Timeframe: Baseline (week 0), week 52

InterventionBeats per minute (beats/min) (Mean)
Semaglutide2.2
Insulin Aspart1.1

Change From Baseline to Week 52 in Waist Circumference

Change from baseline in waist circumference at week 52 is presented. Data is reported for 'on-treatment' observation period: from the date of first dose of trial product (week 0) to the last date on trial product with a visit window of +7 days (week 52). (NCT03689374)
Timeframe: Baseline (week 0), week 52

Interventioncentimeters (cm) (Mean)
Semaglutide-3.3
Insulin Aspart2.1

Daily Basal Insulin Dose at Week 52

Daily basal insulin dose at week 52 is presented. Data is reported for 'on-treatment' observation period: from the date of first dose of trial product (week 0) to the last date on trial product with a visit window of +7 days (week 52). (NCT03689374)
Timeframe: At week 52

InterventionUnits of insulin (Mean)
Semaglutide35.8
Insulin Aspart40.7

Number of Event Adjudication Committee-confirmed Severe (ADA) or Blood Glucose (BG) Confirmed, Symptomatic Hypoglycaemic Episodes (Plasma Glucose Less Than (<) 3.1 mmol/L (56 mg/dL)) From Randomization to Week 52

Number of EAC-confirmed severe or BG confirmed, symptomatic hypoglycaemic episodes (PG <3.1 mmol/L (56 mg/dL)) from randomization (week 0) to week 52 are presented. As per 2013 ADA criteria severe hypoglycaemic episodes were episodes with PG <=3.9 mmol/L (70 mg/dL). Severe or BG confirmed symptomatic hypoglycaemia was an episode, that was BG confirmed by PG value <3.1 mmol/L (56 mg/dL) with symptoms consistent with hypoglycaemia. Data is reported for 'on-treatment' observation period: from the date of first dose of trial product (week 0) to the last date on trial product with a visit window of +7 days (week 52). (NCT03689374)
Timeframe: From randomization (week 0) to week 52

InterventionEpisodes (Number)
Semaglutide254
Insulin Aspart1744

Number of Event Adjudication Committee-confirmed Severe (ADA) or Blood Glucose Confirmed, Symptomatic Hypoglycaemic Episodes (Plasma Glucose <= 3.9 mmol/L (70 mg/dL)) From Randomization to Week 52

Number of EAC-confirmed severe or BG confirmed, symptomatic hypoglycaemic episodes (PG <=3.9 mmol/L (70 mg/dL)) from randomization (week 0) to week 52 are presented. As per 2013 ADA criteria severe hypoglycaemic episodes were episodes with PG <=3.9 mmol/L (70 mg/dL). Severe or BG confirmed symptomatic hypoglycaemia was an episode during which symptoms of hypoglycaemia were not accompanied by a PG determination but that was presumably caused by a PG concentration <= 3.9 mmol/L (70 mg/dL). Data is reported for 'on-treatment' observation period: from the date of first dose of trial product (week 0) to the last date on trial product with a visit window of +7 days (week 52). (NCT03689374)
Timeframe: From randomization (week 0) to week 52

InterventionEpisodes (Number)
Semaglutide1420
Insulin Aspart5616

Number of Event Adjudication Committee-confirmed Severe (ADA) or Clinically Significant Hypoglycaemic Episodes (Plasma Glucose < 3.0 mmol/L (54 mg/dL)) From Randomization to Week 52

Number of EAC-confirmed severe or clinically significant hypoglycaemic episodes (plasma glucose < 3.0 mmol/L (54 mg/dL)) from randomization (week 0) to week 52 are presented. As per 2013 ADA criteria severe hypoglycaemic episodes were episodes with PG <=3.9 mmol/L (70 mg/dL). Severe hypoglycaemia was an episode requiring assistance of another person to actively administer carbohydrate, glucagon or take other corrective actions. Hypoglycaemic episode with plasma glucose < 3.0 mmol/L (54 mg/dL)) was considered as clinically significant. Data is reported for 'on-treatment' observation period: from the date of first dose of trial product (week 0) to the last date on trial product with a visit window of +7 days (week 52). (NCT03689374)
Timeframe: From randomization (week 0) to week 52

InterventionEpisodes (Number)
Semaglutide339
Insulin Aspart2270

Number of Event Adjudication Committee-confirmed Severe Hypoglycaemic Episodes (ADA) From Randomization to Week 52

Number of EAC-confirmed severe hypoglycaemic episodes from randomization (week 0) up to week 52 are presented. As per 2013 ADA criteria severe hypoglycaemic episodes were episodes with PG <=3.9 mmol/L (70 mg/dL). EAC confirmed-severe hypoglycaemia was an episode requiring assistance of another person to actively administer carbohydrate, glucagon or take other corrective actions. Data is reported for 'on-treatment' observation period: from the date of first dose of trial product (week 0) to the last date on trial product with a visit window of +7 days (week 52). (NCT03689374)
Timeframe: From randomization (week 0) to week 52

InterventionEpisodes (Number)
Semaglutide4
Insulin Aspart7

Number of Event Adjudication Committee-confirmed Severe Hypoglycaemic Episodes (ADA) Requiring Hospitalization, Documented Medical Help, or is Life-threatening From Randomization to Week 52

Number of EAC-confirmed severe hypoglycaemic episodes requiring hospitalization, documented medical help, or is life-threatening from randomization (week 0) to week 52 are presented. As per 2013 ADA criteria severe hypoglycaemic episodes were episodes with PG <=3.9 mmol/L (70 mg/dL). Severe hypoglycaemia was an episode requiring assistance of another person to actively administer carbohydrate, glucagon or take other corrective actions. Data is reported for 'on-treatment' observation period: from the date of first dose of trial product (week 0) to the last date on trial product with a visit window of +7 days (week 52). (NCT03689374)
Timeframe: From randomization (week 0) to week 52

InterventionEpisodes (Number)
Semaglutide2
Insulin Aspart4

Time to First Event Adjudication Committee (EAC)-Confirmed Severe Hypoglycaemic Episode American Diabetes Association (ADA) From Randomization up to Week 52

First event per 100 years of exposure time for first EAC confirmed severe hypoglycaemic episodes from randomization (week 0) to week 52 are presented. As per 2013 ADA criteria severe hypoglycaemic episodes were episodes with plasma glucose (PG) less than or equal to (<=) 3.9 millimoles per liter (mmol/L) (70 milligrams per deciliter (mg/dL)). EAC confirmed-severe hypoglycaemia was an episode requiring assistance of another person to actively administer carbohydrate, glucagon or take other corrective actions. Data is reported for 'on-treatment' observation period: from the date of first dose of trial product (week 0) to the last date on trial product with a visit window of +7 days (week 52). (NCT03689374)
Timeframe: From randomization (week 0) up to week 52

InterventionFirst event per 100 years of exposure (Number)
Semaglutide0.4
Insulin Aspart0.7

Time to First Event Adjudication Committee-confirmed Severe Hypoglycaemic Episode (ADA) Requiring Hospitalization, Documented Medical Help, or is Life-threatening Randomization up to Week 52

First event per 100 years of exposure time for first EAC confirmed severe hypoglycaemic episodes requiring hospitalization, documented medical help, or is life threatening from randomization (week 0) to week 52 are presented. As per 2013 ADA criteria severe hypoglycaemic episodes were episodes with PG <=3.9 mmol/L (70 mg/dL). EAC confirmed-severe hypoglycaemia was an episode requiring assistance of another person to actively administer carbohydrate, glucagon or take other corrective actions. Data is reported for 'on-treatment' observation period: from the date of first dose of trial product (week 0) to the last date on trial product with a visit window of +7 days (week 52). (NCT03689374)
Timeframe: From randomization (week 0) up to week 52

InterventionFirst event per 100 years of exposure (Number)
Semaglutide0.2
Insulin Aspart0.4

Total Daily Insulin Dose at Week 52

Total daily insulin dose at week 52 is presented. Data is reported for 'on-treatment' observation period: from the date of first dose of trial product (week 0) to the last date on trial product with a visit window of +7 days (week 52). (NCT03689374)
Timeframe: At week 52

InterventionUnits of insulin (Mean)
Semaglutide35.8
Insulin Aspart77.7

Change From Baseline to Week 52 in 36-item Short Form Health Survey Version 2 (SF-36v2): Total Summary Scores (Physical Component and Mental Component) and Scores From the 8 Domains

SF-36v2 is 36-item patient-reported survey of patient health to measure participant's overall health-related quality of life (HRQoL). It has 36 items: 8 domains of physical, mental health status (physical functioning, role physical health (range:21.23-57.16), bodily pain (range: 21.68-62.00), general health (range: 18.95-66.50), vitality (range: 22.89-70.42), social functioning (range: 17.23-57.34), role emotional problem (range: 14.39-56.17) and mental health (range: 11.63-63.95)) and 2 total summary scores: physical components summary (range: 7.32-70.14) and mental components summary (range: 5.79-69.91) calculated from domain scores. All 10 scores range from 5.79-70.42 . Higher scores indicated a better health state. Change from baseline in SF-36v2, 2 summary and 8 domains scores at week 52 is presented. Data is reported for 'on-treatment' observation period: from date of first dose of trial product (week 0) to last date on trial product with a visit window of +7 days (week 52). (NCT03689374)
Timeframe: Baseline (week 0), week 52

,
InterventionScores on a scale (Mean)
Physical Component SummaryMental Component SummaryPhysical FunctioningRole Physical HealthBodily PainGeneral HealthVitalitySocial FunctioningRole Emotional ProblemMental Health
Insulin Aspart0.4-0.30.2-0.20.80.30.1-0.6-0.20.1
Semaglutide1.40.11.40.11.51.61.10.20.00.6

Change From Baseline to Week 52 in Diabetes Quality of Life Clinical Trial Questionnaire (DQLCTQ-R): Scores From the 8 Domains

The DQLCTQ-R questionnaire was used to assess participants' HRQoL. The DQLCTQ-R questionnaire contains 57 items and measures and provide scores for the 8 domains (physical function, energy or fatigue, health distress, mental health, satisfaction, treatment satisfaction, treatment flexibility and frequency of symptoms). The 8 domain scores related to DQLCTQ-R are measured on a scale from 0-100. For all scores, higher values indicated better health status. Change from baseline in DQLCTQ-R 8 domain scores at week 52 is presented. Data is reported for 'on-treatment' observation period: from the date of first dose of trial product (week 0) to the last date on trial product with a visit window of +7 days (week 52). (NCT03689374)
Timeframe: Baseline (week 0), week 52

,
InterventionScores on a scale (Mean)
Physical functionEnergy or fatigueHealth distressMental healthSatisfactionTreatment satisfactionTreatment flexibilityFrequency of symptoms
Insulin Aspart-0.40.40.30.5-0.20.8-1.21.8
Semaglutide2.42.3-0.27.24.19.94.24.1

Change From Baseline to Week 52 in Systolic and Diastolic Blood Pressure

Change from baseline in systolic and diastolic blood pressure at week 52 are presented. Data is reported for 'on-treatment' observation period: from the date of first dose of trial product (week 0) to the last date on trial product with a visit window of +7 days (week 52). (NCT03689374)
Timeframe: Baseline (week 0), week 52

,
Interventionmillimeter of mercury (mmHg) (Mean)
Diastolic Blood PressureSystolic Blood Pressure
Insulin Aspart-0.41.0
Semaglutide-1.4-2.8

Change in Body Weight at Week 30

Change from Baseline to Week 30 in body weight (NCT03353350)
Timeframe: Baseline to Week 30

Interventionkg (Mean)
Placebo-1.35
Efpeglenatide 2 mg-1.01
Efpeglenatide 4 mg-3.34
Efpeglenatide 6 mg-3.19

Change in Body Weight at Week 56

Change from Baseline to Week 56 in body weight (NCT03353350)
Timeframe: Baseline to Week 56

Interventionkg (Mean)
Placebo-1.26
Efpeglenatide 2 mg-0.94
Efpeglenatide 4 mg-3.24
Efpeglenatide 6 mg-1.82

Change in Fasting Plasma Glucose (FPG)

Change from Baseline to Week 30 in FPG (NCT03353350)
Timeframe: Baseline to Week 30

InterventionFPG (mmol/L) (Mean)
Placebo8.59
Efpeglenatide 2 mg-0.87
Efpeglenatide 4 mg6.84
Efpeglenatide 6 mg6.55

Change in Glycated Hemoglobin (HbA1c) (%)

Change from Baseline to Week 30 in HbA1c (NCT03353350)
Timeframe: Baseline to Week 30

InterventionHbA1c (%) (Mean)
Placebo-0.46
Efpeglenatide 2 mg-1.14
Efpeglenatide 4 mg-1.48
Efpeglenatide 6 mg-1.59

Change in HbA1c (%)

Change from Baseline to Week 56 in HbA1c (NCT03353350)
Timeframe: Baseline to Week 56

InterventionHbA1c (%) (Mean)
Placebo-0.52
Efpeglenatide 2 mg-1.18
Efpeglenatide 4 mg-1.51
Efpeglenatide 6 mg-1.51

HbA1c <7%

Number of participants with HbA1c <7.0% at Week 30 (NCT03353350)
Timeframe: Week 30

InterventionParticipants (Count of Participants)
Placebo26
Efpeglenatide 2 mg60
Efpeglenatide 4 mg66
Efpeglenatide 6 mg76

Hypoglycemic Events

Number of hypoglycemic events (NCT03353350)
Timeframe: Baseline to Week 56

InterventionNumber of events (Number)
Placebo2
Efpeglenatide 2 mg10
Efpeglenatide 4 mg14
Efpeglenatide 6 mg14

Hypoglycemic Participants

Number of participants with at least 1 hypoglycemic event during treatment period (NCT03353350)
Timeframe: Baseline to Week 56

InterventionParticipants (Count of Participants)
Placebo2
Efpeglenatide 2 mg10
Efpeglenatide 4 mg14
Efpeglenatide 6 mg14

Treatment Emergent Adverse Events (TEAEs)

Number of participants with TEAEs (NCT03353350)
Timeframe: Baseline to Week 56

InterventionNumber of Treatment Emergent AEs (Number)
Placebo79
Efpeglenatide 2 mg80
Efpeglenatide 4 mg79
Efpeglenatide 6 mg83

Change in Body Weight (kg) (Week 52)

Change from baseline (week 0) in body weight to week 52. The endpoint was evaluated based on data from the in-trial observation period. In trial observation period started at the date of randomisation and included the period after initiation of rescue medication and/or premature trial product discontinuation, if any. (NCT03021187)
Timeframe: Week 0, week 52

InterventionKg (Mean)
Oral Semaglutide 3 mg-0.9
Oral Semaglutide 7 mg-2.2
Oral Semaglutide 14 mg-3.8
Placebo0.5

Change in HbA1c (Week 52)

Change from baseline (week 0) in HbA1c to week 52. The endpoint was evaluated based on data from the in-trial observation period. In trial observation period started at the date of randomisation and included the period after initiation of rescue medication and/or premature trial product discontinuation, if any. (NCT03021187)
Timeframe: Week 0, week 52

InterventionPercentage of HbA1c (Mean)
Oral Semaglutide 3 mg-0.6
Oral Semaglutide 7 mg-0.9
Oral Semaglutide 14 mg-1.2
Placebo-0.2

Number of Treatment-emergent Adverse Events (TEAEs) During Exposure to Trial Product

Treatment emergent adverse events (TEAEs) were recorded from week 0 to week 57 (52-week treatment period plus the 5-week follow-up period). Adverse events (AEs) with onset during the on-treatment observation period were considered treatment-emergent. On-treatment observation period was defined as the time period when a participant was on treatment with trial product, including any period after initiation of rescue medication. (NCT03021187)
Timeframe: Weeks 0-57

InterventionEvents (Number)
Oral Semaglutide 3 mg626
Oral Semaglutide 7 mg555
Oral Semaglutide 14 mg586
Placebo464

Number of Treatment-emergent Severe or BG-confirmed Symptomatic Hypoglycaemic Episodes

Treatment emergent severe or BG confirmed symptomatic hypoglycaemic episodes were recorded during week 0 to week 57 (52-week treatment period plus the 5-week follow-up period). Hypoglycaemic episodes with onset during the on-treatment observation period were considered treatment-emergent. On-treatment observation period was defined as the time period when a subject was on treatment with trial product, including any period after initiation of rescue medication. Severe hypoglycaemia was defined as an episode requiring assistance of another person to actively administer carbohydrate or glucagon, or take other corrective actions. BG-confirmed symptomatic hypoglycaemia: Confirmed by a glucose value <3.1 mmol/L (56 mg/dL) with symptoms consistent with hypoglycaemia. (NCT03021187)
Timeframe: Weeks 0-57

InterventionEpisodes (Number)
Oral Semaglutide 3 mg196
Oral Semaglutide 7 mg180
Oral Semaglutide 14 mg147
Placebo156

Participants With Treatment-emergent Severe or BG-confirmed Symptomatic Hypoglycaemic Episodes

Treatment emergent severe or BG confirmed symptomatic hypoglycaemic episodes were recorded during week 0 to week 57 (52-week treatment period plus the 5-week follow-up period). Hypoglycaemic episodes with onset during the on-treatment observation period were considered treatment-emergent. On-treatment observation period was defined as the time period when a subject was on treatment with trial product, including any period after initiation of rescue medication. Severe hypoglycaemia was defined as an episode requiring assistance of another person to actively administer carbohydrate or glucagon, or take other corrective actions. BG-confirmed symptomatic hypoglycaemia: Confirmed by a glucose value <3.1 mmol/L (56 mg/dL) with symptoms consistent with hypoglycaemia. (NCT03021187)
Timeframe: Weeks 0-57

InterventionParticipants (Count of Participants)
Oral Semaglutide 3 mg52
Oral Semaglutide 7 mg47
Oral Semaglutide 14 mg48
Placebo54

Change in Amylase - Ratio to Baseline

Change from baseline (week 0) in amylase (units/litre (U/L)) at weeks 26 and 52 is presented as ratio to baseline. Results are based on the data from the on-treatment observation period which was the time period when a participant was on treatment with trial product, including any period after initiation of rescue medication. (NCT03021187)
Timeframe: Week 0, week 26, week 52

,,,
InterventionRatio of amylase (Geometric Mean)
Week 26Week 52
Oral Semaglutide 14 mg1.141.17
Oral Semaglutide 3 mg1.081.07
Oral Semaglutide 7 mg1.121.11
Placebo1.010.99

Change in Body Mass Index

Change from baseline (week 0) in body mass index (BMI) was evaluated at weeks 26 and 52. BMI was calculated based on body weight and height based on the formula: BMI kg/m^2 = body weight (kg)/(Height (m) x Height (m)). Data based on in-trial observation period is presented. In trial observation period started at the date of randomisation and included the period after initiation of rescue medication and/or premature trial product discontinuation, if any. (NCT03021187)
Timeframe: Week 0, week 26, week 52

,,,
Interventionkg/m^2 (Mean)
Week 26Week 52
Oral Semaglutide 14 mg-1.4-1.4
Oral Semaglutide 3 mg-0.5-0.3
Oral Semaglutide 7 mg-1.0-0.8
Placebo-0.20.2

Change in Body Weight (Percentage)

Relative change from baseline (week 0) in body weight (%) was evaluated at weeks 26 and 52.The endpoint was evaluated based on data from the in-trial observation period. In trial observation period started at the date of randomisation and included the period after initiation of rescue medication and/or premature trial product discontinuation, if any. (NCT03021187)
Timeframe: Week 0, week 26, week 52

,,,
InterventionPercentage change (Mean)
Week 26Week 52
Oral Semaglutide 14 mg-4.30-4.42
Oral Semaglutide 3 mg-1.73-1.18
Oral Semaglutide 7 mg-3.11-2.54
Placebo-0.470.65

Change in Body Weight (Week 26)

Change from baseline (week 0) in body weight was evaluated at week 26. The endpoint was evaluated based on data from the in-trial observation period. In-trial observation period started at the date of randomisation and included the period after initiation of rescue medication and/or premature trial product discontinuation, if any. The endpoint was also evaluated based on data from the on-treatment without rescue medication observation period. It started at the date of first dose of trial product and excluded the period after initiation of rescue medication and/or premature trial product discontinuation, if any. (NCT03021187)
Timeframe: Week 0, week 26

,,,
InterventionKg (Mean)
In trialOn-treatment without rescue medication
Oral Semaglutide 14 mg-3.7-3.9
Oral Semaglutide 3 mg-1.4-1.5
Oral Semaglutide 7 mg-2.6-3.0
Placebo-0.5-0.5

Change in DTSQs: Individual Items and Treatment Satisfaction Score (6 of the 8 Items Summed)

"Change from baseline (week 0) in Diabetes Treatment Satisfaction Questionnaire - status version (DTSQs) was evaluated at week 26 and week 52. The DTSQs items are scored on a 7-point graded response scale ranging from 6 to 0. Higher scores indicate higher levels of treatment satisfaction for DTSQs items 1, 4 -8. For items 2 and 3 a higher score indicates a higher patient perceived experience of hyperglycaemia and hypoglycaemia, respectively. Thus, lower scores indicate a perception of blood glucose levels being none of the time unacceptably high (item 2) or low (item 3). The domain score of total treatment satisfaction (total treatment satisfaction score) was computed by adding the six items scores 1, 4-8. The score has a minimum of 0 and a maximum of 36. A higher treatment satisfaction score indicates a higher level of treatment satisfaction." (NCT03021187)
Timeframe: Week 0, week 26, week 52

,,,
InterventionScore on a scale (Mean)
Satisfaction with treatment: wk 26Satisfaction with treatment: wk 52Feeling of unacceptably high blood sugars: wk 26Feeling of unacceptably high blood sugars: wk 52Feeling of unacceptably low blood sugars: wk 26Feeling of unacceptably low blood sugars: wk 52Convenience of treatment: wk 26Convenience of treatment: wk 52Flexibility of treatment: wk 26Flexibility of treatment: wk 52Satisfaction with understading of diabetes: wk 26Satisfaction with understading of diabetes: wk 52Recommending treatment to others: wk 26Recommending treatment to others: wk 52Satisfaction to continue present treatment: wk 26Satisfaction to continue present treatment: wk 52Total treatment satisfaction: wk 26Total treatmemt satisfaction: wk 52
Oral Semaglutide 14 mg0.630.78-1.29-1.340.13-0.060.500.440.400.460.270.340.530.650.580.652.903.32
Oral Semaglutide 3 mg0.470.53-0.62-0.700.070.040.510.380.310.250.240.250.200.320.400.412.122.14
Oral Semaglutide 7 mg0.590.51-1.23-1.15-0.06-0.100.500.520.370.420.310.350.660.630.570.563.002.99
Placebo0.180.20-0.28-0.41-0.15-0.020.200.190.230.230.040.030.02-0.010.090.030.760.67

Change in ECG Evaluation

Change from baseline (week 0) in electrocardiogram (ECG) was evaluated at weeks 26 and 52. Change from baseline results are presented as shift in findings (normal; abnormal and not clinically significant (NCS); abnormal and clinically significant (CS)) from week 0 to week 26 and 52. Results are based on the data from the in-trial observation period, which was the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of rescue medication and/or premature discontinuation of trial product. (NCT03021187)
Timeframe: Week 0, week 26, week 52

,,,
InterventionParticipants (Count of Participants)
Normal (week 0) to Normal (week 26)Normal (week 0) to Abnormal NCS (week 26)Normal (week 0) to Abnormal CS (week 26)Abnormal NCS (week 0) to Normal (week 26)Abnormal NCS (week 0) to Abnormal NCS (week 26)Abnormal NCS (week 0) to Abnormal CS (week 26)Abnormal CS (week 0) to Normal (week 26)Abnormal CS (week 0) to Abnormal NCS (week 26)Abnormal CS (week 0) to Abnormal CS (week 26)Normal (week 0) to Normal (week 52)Normal (week 0) to Abnormal NCS (week 52)Normal (week 0) to Abnormal CS (week 52)Abnormal NCS to Normal (Week 52)Abnormal NCS to Abnormal NCS (Week 52)Abnormal NCS to Abnormal CS (Week 52)Abnormal CS to Normal (Week 52)Abnormal CS to Abnormal NCS (Week 52)Abnormal CS to Abnormal CS (Week 52)
Oral Semaglutide 14 mg90170164701118520119420021
Oral Semaglutide 3 mg101100224400009514213500000
Oral Semaglutide 7 mg98120174200049115217401004
Placebo93120195101018417121471011

Change in Fasting Plasma Glucose (FPG)

Change from baseline (week 0) in FPG to week 26 and week 52. The endpoint was evaluated based on data from the in-trial observation period. In trial observation period started at the date of randomisation and included the period after initiation of rescue medication and/or premature trial product discontinuation, if any. (NCT03021187)
Timeframe: Week 0, week 26, week 52

,,,
Interventionmmol/L (Mean)
Week 26Week 52
Oral Semaglutide 14 mg-1.36-1.60
Oral Semaglutide 3 mg-0.45-0.81
Oral Semaglutide 7 mg-1.14-1.12
Placebo0.51-0.09

Change in HbA1c (Week 26)

Change from baseline (week 0) in glycosylated haemoglobin (HbA1c) was evaluated at week 26. The endpoint was evaluated based on data from the in-trial observation period. In-trial observation period started at the date of randomisation and included the period after initiation of rescue medication and/or premature trial product discontinuation, if any. The endpoint was also analysed based on data from the on-treatment without rescue medication observation period. On-treatment without rescue medication observation period started at the date of the first dose of trial product and includes the period after initiation of rescue medication, if any, and excludes the period after premature trial discontinuation, if any. (NCT03021187)
Timeframe: Week 0, week 26

,,,
InterventionPercentage of HbA1c (Mean)
In-trialOn-treatment without rescue medication
Oral Semaglutide 14 mg-1.3-1.4
Oral Semaglutide 3 mg-0.5-0.6
Oral Semaglutide 7 mg-1.0-1.1
Placebo-0.1-0.1

Change in HDL Cholesterol - Ratio to Baseline

Change from baseline (week 0) in HDL cholesterol (mmol/L) at weeks 26 and 52 is presented as ratio to baseline. Results are based on the data from the in-trial observation period. In trial observation period started at the date of randomisation and included the period after initiation of rescue medication and/or premature trial product discontinuation, if any. (NCT03021187)
Timeframe: Week 0, week 26, week 52

,,,
InterventionRatio of HDL cholesterol (Geometric Mean)
Week 26Week 52
Oral Semaglutide 14 mg0.981.01
Oral Semaglutide 3 mg1.001.01
Oral Semaglutide 7 mg0.980.98
Placebo1.011.00

Change in IWQoL-Lite-CT: Total Score and Scores From the 4 Domains

The Impact of Weight on Quality of Life Clinical Trials Version (IWQOL-Lite-CT) is designed to assess the impact of changes in weight on patients' quality of life within the context of clinical trials. The items of the IWQOL-Lite-CT pertain to physical functioning (physical, physical function and pain/discomfort) and psychosocial domains and all items employ a 5-point graded response scale (never, rarely, sometimes, usually, always; or not at all true, a little true, moderately true, mostly true, completely true). All IWQOL-Lite-CT composite scores range from 0 to 100, with higher scores reflecting better levels of functioning. Results are based on the data from the in-trial observation period, which started at the date of randomisation and included the period after initiation of rescue medication and/or premature trial product discontinuation, if any. (NCT03021187)
Timeframe: Week 0, week 26, week 52

,,,
InterventionScore on a scale (Mean)
1) Psychosocial (Week 26)1) Psychosocial (Week 52)2) Physical (Week 26)2) Physical (Week 52)3) Physical function(Week 26)3) Physical function(Week 52)4) Pain/discomfort (Week 26)4) Pain/discomfort (Week 52)5) IWQOL-Lite-CT Total (Week 26)5) IWQOL-Lite-CT Total (Week 52)
Oral Semaglutide 14 mg4.105.352.152.502.512.591.232.283.414.35
Oral Semaglutide 3 mg1.451.962.293.101.883.453.302.231.742.35
Oral Semaglutide 7 mg-0.32-0.92-0.66-0.53-0.35-0.59-1.45-0.37-0.45-0.79
Placebo-0.49-0.46-1.75-1.24-1.70-0.98-1.85-1.88-0.94-0.73

Change in LDL Cholesterol - Ratio to Baseline

Change from baseline in LDL cholesterol (mmol/L) is presented as ratio to baseline at week 26 and week 52. Results are based on the data from the in-trial observation period. In trial observation period started at the date of randomisation and included the period after initiation of rescue medication and/or premature trial product discontinuation, if any. (NCT03021187)
Timeframe: Week 0, week 26, week 52

,,,
InterventionRatio of LDL cholesterol (Geometric Mean)
Week 26Week 52
Oral Semaglutide 14 mg0.930.95
Oral Semaglutide 3 mg0.980.97
Oral Semaglutide 7 mg0.930.96
Placebo1.031.00

Change in Lipase - Ratio to Baseline

Change from baseline (week 0) in lipase (units/litre (U/L)) at weeks 26 and 52 is presented as ratio to baseline. Results are based on the data from the on-treatment observation period which was the time period when a participant was on treatment with trial product, including any period after initiation of rescue medication (NCT03021187)
Timeframe: Week 0, week 26, week 52

,,,
InterventionRatio of lipase (Geometric Mean)
Week 26Week 52
Oral Semaglutide 14 mg1.351.35
Oral Semaglutide 3 mg1.141.09
Oral Semaglutide 7 mg1.341.25
Placebo0.990.99

Change in Pulse Rate

Change from baseline (week 0) in pulse rate was evaluated at weeks 26 and 52 Results are based on the data from the on-treatment observation period which was the time period when a participant was on treatment with trial product, including any period after initiation of rescue medication. (NCT03021187)
Timeframe: Week 0, week 26, week 52

,,,
InterventionBeats/minute (Mean)
Week 26Week 52
Oral Semaglutide 14 mg32
Oral Semaglutide 3 mg1-0
Oral Semaglutide 7 mg21
Placebo-00

Change in SBP and DBP

Change from baseline (week 0) in systolic blood pressure (SBP) and diastolic blood pressure (DBP) was evaluated at weeks 26 and 52 Results are based on the data from the on-treatment observation period which was the time period when a participant was on treatment with trial product, including any period after initiation of rescue medication. (NCT03021187)
Timeframe: Week 0, week 26, week 52

,,,
InterventionmmHg (Mean)
SBP: Week 26SBP: Week 52DBP: Week 26DBP: Week 52
Oral Semaglutide 14 mg-5-6-1-2
Oral Semaglutide 3 mg-1-1-0-1
Oral Semaglutide 7 mg-3-3-1-2
Placebo100-0

Change in Self-measured Plasma Glucose (SMPG) Mean 7-point Profile

Change from baseline (week 0) in self-measured plasma glucose (SMPG) mean 7-point profile to week 26 and week 52. SMPG was recorded at the following 7 time points: before breakfast, 90 minutes after start of breakfast, before lunch, 90 minutes after start of lunch, before dinner, 90 minutes after dinner and at bedtime. Mean 7-point profile was defined as the area under the profile, calculated using the trapezoidal method, divided by the measurement time. The endpoint was evaluated based on data from the in-trial observation period. In trial observation period started at the date of randomisation and included the period after initiation of rescue medication and/or premature trial product discontinuation, if any. (NCT03021187)
Timeframe: Week 0, week 26, week 52

,,,
Interventionmmol/L (Mean)
Week 26Week 52
Oral Semaglutide 14 mg-2.0-2.0
Oral Semaglutide 3 mg-1.2-1.6
Oral Semaglutide 7 mg-1.8-1.7
Placebo-0.3-0.9

Change in SF-36v2 (Acute Version) Health Survey: Scores From the 8 Domains, the Physical Component Summary (PCS) and the Mental Component Summary (MCS)

SF-36 is a 36-item patient-reported survey of patient health that measures the participant's overall health-related quality of life (HRQoL). SF-36v2™ (acute version) questionnaire measured eight domains of functional health and well-being as well as two component summary scores (physical component summary (PCS) and mental component summary (MCS)). The 0-100 scale scores (where higher scores indicated a better HRQoL) from the SF-36 were converted to norm-based scores to enable a direct interpretation in relation to the distribution of the scores in the 2009 U.S. general population. In the metric of norm-based scores, 50 and 10 corresponds to the mean and standard deviation respectively of the 2009 U.S. general population. Change from baseline (week 0) in the domain scores and component summary (PCS and MCS) scores were evaluated at weeks 26 and 52. A positive change score indicates an improvement since baseline. Results are based on the data from the in-trial observation period. (NCT03021187)
Timeframe: Week 0, week 26, week 52

,,,
InterventionScore on a scale (Mean)
1) Physical functioning (Week 26)1) Physical functioning (Week 52)2) Role Physical (Week 26)2) Role Physical (Week 52)3) Bodily Pain (Week 26)3) Bodily Pain (Week 52)4) General Health (Week 26)4) General Health (Week 52)5) Vitality (Week 26)5) Vitality (Week 52)6) Social functioning (Week 26)6) Social functioning (Week 52)7) Role emotional (Week 26)7) Role emotional (Week 52)8) Mental health (Week 26)8) Mental health (Week 52)9) Physical component summary (Week 26)9) Physical component summary (Week 52)10) Mental component summary (Week 26)10) Mental component summary (Week 52)
Oral Semaglutide 14 mg-0.07-0.320.04-0.87-0.18-0.211.261.380.140.70-0.510.030.240.090.990.89-0.02-0.360.490.82
Oral Semaglutide 3 mg0.530.51-0.320.00-0.02-0.401.430.92-0.56-0.53-0.310.11-0.940.77-1.41-0.480.940.26-1.41-0.09
Oral Semaglutide 7 mg0.52-0.40-0.43-0.761.470.560.700.75-1.27-1.430.34-0.610.62-0.34-0.82-0.740.750.12-0.55-0.89
Placebo-0.82-0.77-0.39-0.93-0.72-0.64-0.36-1.43-1.69-1.09-1.10-1.74-1.50-2.78-2.32-1.30-0.05-0.41-2.16-2.19

Change in SMPG Mean Postprandial Increment Over All Meals

Change from baseline (week 0) in SMPG mean postprandial increment over all meals to week 26 and week 52. The endpoint was evaluated based on data from the in-trial observation period. In trial observation period started at the date of randomisation and included the period after initiation of rescue medication and/or premature trial product discontinuation, if any. (NCT03021187)
Timeframe: Week 0, week 26, week 52

,,,
Interventionmmol/L (Mean)
Week 26Week 52
Oral Semaglutide 14 mg-1.2-0.7
Oral Semaglutide 3 mg-0.3-0.3
Oral Semaglutide 7 mg-0.8-0.7
Placebo-0.1-0.3

Change in Total Cholesterol - Ratio to Baseline

Change from baseline in total cholesterol (mmol/L) is presented as ratio to baseline at week 26 and week 52. Results are based on the data from the in-trial observation period. In trial observation period started at the date of randomisation and included the period after initiation of rescue medication and/or premature trial product discontinuation, if any. (NCT03021187)
Timeframe: Week 0, week 26, week 52

,,,
InterventionRatio of total cholesterol (Geometric Mean)
Week 26Week 52
Oral Semaglutide 14 mg0.950.95
Oral Semaglutide 3 mg0.990.98
Oral Semaglutide 7 mg0.950.97
Placebo1.031.00

Change in Total Daily Insulin Dose

Change from baseline in total daily insulin dose to week 26 and week 52 is presented. Results are based on the data from the in-trial observation period. In trial observation period started at the date of randomisation and included the period after initiation of rescue medication and/or premature trial product discontinuation, if any. (NCT03021187)
Timeframe: Week 0, week 26, week 52

,,,
InterventionUnits/day (Mean)
Week 26Week 52
Oral Semaglutide 14 mg-8-5
Oral Semaglutide 3 mg-51
Oral Semaglutide 7 mg-9-8
Placebo-28

Change in Triglycerides - Ratio to Baseline

Change from baseline (week 0) in triglycerides (mmol/L) at weeks 26 and 52 is presented as ratio to baseline. Results are based on the data from the in-trial observation period. In trial observation period started at the date of randomisation and included the period after initiation of rescue medication and/or premature trial product discontinuation, if any. (NCT03021187)
Timeframe: Week 0, week 26, week 52

,,,
InterventionRatio of triglycerides (Geometric Mean)
Week 26Week 52
Oral Semaglutide 14 mg0.910.86
Oral Semaglutide 3 mg0.970.93
Oral Semaglutide 7 mg0.920.94
Placebo0.990.97

Change in Waist Circumference

Change from baseline (week 0) in waist circumference was evaluated at weeks 26 and 52.The endpoint was evaluated based on data from the in-trial observation period. In trial observation period started at the date of randomisation and included the period after initiation of rescue medication and/or premature trial product discontinuation, if any. (NCT03021187)
Timeframe: Week 0, week 26, week 52

,,,
Interventioncm (Mean)
Week 26Week 52
Oral Semaglutide 14 mg-3.6-4.0
Oral Semaglutide 3 mg-0.9-0.8
Oral Semaglutide 7 mg-2.3-2.3
Placebo-0.60.3

Semaglutide Plasma Concentrations for Population PK Analyses

This outcome measure is only applicable for the oral semaglutide treatment arms (3 mg, 7 mg and 14 mg). Semaglutide plasma concentrations were measured at week 4, 14, 26, 38 and 52. Results are based on the data from the on-treatment observation period which was the time period when a participant was on treatment with trial product, including any period after initiation of rescue medication. (NCT03021187)
Timeframe: Weeks 0-52

,,
Interventionnmol/L (Geometric Mean)
Week 4Week 14Week 26Week 38Week 52
Oral Semaglutide 14 mg2.914.512.610.811.9
Oral Semaglutide 3 mg2.92.92.72.52.4
Oral Semaglutide 7 mg2.97.57.26.95.8

Time to Additional Anti-diabetic Medication

Presented results are the number of participants who had taken additional anti-diabetic medication anytime during the periods, from week 0 to week 26 and week 0 to week 52. Additional anti-diabetic medication was defined as use of new anti-diabetic medication for more than 21 days with the initiation at or after randomisation (week 0) and before (planned) end-of-treatment (week 52), and/or intensification of anti-diabetic medication (a more than 20% increase in dose relative to baseline) for more than 21 days with the intensification at or after randomisation and before (planned) end-of-treatment. Results are based on the data from the in-trial observation period, which was the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of rescue medication and/or premature discontinuation of trial product. (NCT03021187)
Timeframe: Weeks 0-52

,,,
InterventionParticipants (Count of Participants)
Week 0-26Week 0-52
Oral Semaglutide 14 mg844
Oral Semaglutide 3 mg961
Oral Semaglutide 7 mg845
Placebo1175

Time to Rescue Medication

Presented results are the number of participants who had taken rescue medication anytime during the periods, from week 0 to week 26 and week 0 to week 52. Rescue medication was defined as use of new anti-diabetic medication as add-on to trial product and used for more than 21 days with the initiation at or after randomisation (week 1) and before last day on trial product, and/or intensification of anti-diabetic medication (a more than 20% increase in dose relative to baseline) for more than 21 days with the intensification at or after randomisation and before last day on trial product. Results are based on the data from the on-treatment without rescue medication observation period, which was the time period when a participant was on treatment with trial product, excluding any period after initiation of rescue medication and/or premature trial product discontinuation. (NCT03021187)
Timeframe: Weeks 0-52

,,,
InterventionParticipants (Count of Participants)
Week 0-26Week 0-52
Oral Semaglutide 14 mg431
Oral Semaglutide 3 mg554
Oral Semaglutide 7 mg233
Placebo967

Change in Eye Examination Category

Participants with eye examination (fundoscopy) findings, normal, abnormal NCS and abnormal CS at baseline (week -2) and week 52 are presented. Results are based on the data from the in-trial observation period, which was the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of rescue medication and/or premature discontinuation of trial product. (NCT03021187)
Timeframe: Week -2, week 52

InterventionParticipants (Count of Participants)
Left eye (week -2)72577392Left eye (week -2)72577393Left eye (week -2)72577394Left eye (week -2)72577395Left eye (week 52)72577392Left eye (week 52)72577393Left eye (week 52)72577394Left eye (week 52)72577395Right eye (week -2)72577392Right eye (week -2)72577393Right eye (week -2)72577394Right eye (week -2)72577395Right eye (week 52)72577392Right eye (week 52)72577393Right eye (week 52)72577394Right eye (week 52)72577395
NormalAbnormal NCSAbnormal CS
Oral Semaglutide 3 mg89
Placebo108
Oral Semaglutide 7 mg64
Placebo55
Oral Semaglutide 3 mg19
Placebo21
Oral Semaglutide 3 mg83
Oral Semaglutide 7 mg102
Oral Semaglutide 14 mg92
Placebo88
Oral Semaglutide 3 mg65
Oral Semaglutide 7 mg51
Oral Semaglutide 14 mg52
Placebo53
Oral Semaglutide 3 mg22
Placebo25
Oral Semaglutide 3 mg85
Oral Semaglutide 7 mg104
Oral Semaglutide 14 mg99
Placebo106
Oral Semaglutide 3 mg76
Oral Semaglutide 7 mg63
Oral Semaglutide 14 mg64
Placebo58
Oral Semaglutide 7 mg13
Oral Semaglutide 14 mg18
Placebo20
Oral Semaglutide 3 mg79
Oral Semaglutide 7 mg99
Oral Semaglutide 14 mg97
Placebo90
Oral Semaglutide 3 mg67
Oral Semaglutide 7 mg54
Oral Semaglutide 14 mg51
Placebo50
Oral Semaglutide 3 mg23
Oral Semaglutide 7 mg14
Oral Semaglutide 14 mg15
Placebo26

Change in Physical Examination

Participants with physical examination findings, normal, abnormal NCS and abnormal CS at baseline (weeks -2) and weeks 52 presented. Results are based on the data from the in-trial observation period, which was the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of rescue medication and/or premature discontinuation of trial product. Results are presented for the following examinations: 1) Cardiovascular system; 2) Central and peripheral nervous system; 3) Gastrointestinal system, incl. mouth; 4) General appearance; 5) Head, ears, eyes, nose, throat, neck; 6) Lymph node palpation; 7) Musculoskeletal system; 8) Respiratory system; 9) Skin; 10) Thyroid gland. (NCT03021187)
Timeframe: Week -2, week 52

InterventionParticipants (Count of Participants)
1) Cardiovascular system (week -2)725773921) Cardiovascular system (week -2)725773931) Cardiovascular system (week -2)725773941) Cardiovascular system (week -2)725773951) Cardiovascular system (week 52)725773921) Cardiovascular system (week 52)725773931) Cardiovascular system (week 52)725773941) Cardiovascular system (week 52)725773952) Central and peripheral nervous system (week -2)725773922) Central and peripheral nervous system (week -2)725773952) Central and peripheral nervous system (week -2)725773932) Central and peripheral nervous system (week -2)725773942) Central and peripheral nervous system (week 52)725773922) Central and peripheral nervous system (week 52)725773932) Central and peripheral nervous system (week 52)725773942) Central and peripheral nervous system (week 52)725773953) Gastrointestinal system, incl. mouth (week -2)725773933) Gastrointestinal system, incl. mouth (week -2)725773953) Gastrointestinal system, incl. mouth (week -2)725773923) Gastrointestinal system, incl. mouth (week -2)725773943) Gastrointestinal system, incl. mouth (week 52)725773923) Gastrointestinal system, incl. mouth (week 52)725773933) Gastrointestinal system, incl. mouth (week 52)725773953) Gastrointestinal system, incl. mouth (week 52)725773944) General appearance (week -2)725773924) General appearance (week -2)725773934) General appearance (week -2)725773944) General appearance (week -2)725773954) General appearance (week 52)725773924) General appearance (week 52)725773934) General appearance (week 52)725773944) General appearance (week 52)725773955) Head, ears, eyes, nose, throat, neck (week -2)725773925) Head, ears, eyes, nose, throat, neck (week -2)725773935) Head, ears, eyes, nose, throat, neck (week -2)725773945) Head, ears, eyes, nose, throat, neck (week -2)725773955) Head, ears, eyes, nose, throat, neck (week 52)725773925) Head, ears, eyes, nose, throat, neck (week 52)725773935) Head, ears, eyes, nose, throat, neck (week 52)725773945) Head, ears, eyes, nose, throat, neck (week 52)725773956) Lymph node palpation (week -2)725773926) Lymph node palpation (week -2)725773936) Lymph node palpation (week -2)725773946) Lymph node palpation (week -2)725773956) Lymph node palpation (week 52)725773926) Lymph node palpation (week 52)725773936) Lymph node palpation (week 52)725773946) Lymph node palpation (week 52)725773957) Musculoskeletal system (week -2)725773927) Musculoskeletal system (week -2)725773937) Musculoskeletal system (week -2)725773957) Musculoskeletal system (week -2)725773947) Musculoskeletal system (week 52)725773927) Musculoskeletal system (week 52)725773937) Musculoskeletal system (week 52)725773947) Musculoskeletal system (week 52)725773958) Respiratory system (week -2)725773928) Respiratory system (week -2)725773938) Respiratory system (week -2)725773948) Respiratory system (week -2)725773958) Respiratory system (week 52)725773928) Respiratory system (week 52)725773938) Respiratory system (week 52)725773948) Respiratory system (week 52)725773959) Skin (week -2)725773929) Skin (week -2)725773939) Skin (week -2)725773949) Skin (week -2)725773959) Skin (week 52)725773929) Skin (week 52)725773939) Skin (week 52)725773949) Skin (week 52)7257739510) Thyroid gland (week -2)7257739310) Thyroid gland (week -2)7257739210) Thyroid gland (week -2)7257739410) Thyroid gland (week -2)7257739510) Thyroid gland (week 52)7257739310) Thyroid gland (week 52)7257739210) Thyroid gland (week 52)7257739410) Thyroid gland (week 52)72577395
Abnormal NCSNormalAbnormal CS
Oral Semaglutide 3 mg166
Oral Semaglutide 7 mg166
Oral Semaglutide 14 mg157
Placebo170
Oral Semaglutide 3 mg18
Oral Semaglutide 7 mg15
Placebo14
Oral Semaglutide 3 mg157
Oral Semaglutide 7 mg158
Oral Semaglutide 14 mg145
Placebo160
Oral Semaglutide 3 mg17
Oral Semaglutide 7 mg12
Oral Semaglutide 14 mg24
Placebo12
Oral Semaglutide 3 mg158
Oral Semaglutide 7 mg157
Oral Semaglutide 14 mg158
Placebo163
Oral Semaglutide 3 mg26
Oral Semaglutide 7 mg24
Oral Semaglutide 3 mg149
Oral Semaglutide 7 mg150
Oral Semaglutide 14 mg147
Oral Semaglutide 3 mg25
Oral Semaglutide 7 mg20
Oral Semaglutide 14 mg22
Oral Semaglutide 7 mg175
Oral Semaglutide 14 mg177
Placebo180
Oral Semaglutide 14 mg4
Placebo4
Oral Semaglutide 3 mg163
Oral Semaglutide 14 mg166
Placebo171
Oral Semaglutide 3 mg9
Oral Semaglutide 3 mg159
Oral Semaglutide 7 mg162
Oral Semaglutide 14 mg160
Oral Semaglutide 7 mg18
Oral Semaglutide 14 mg21
Placebo22
Oral Semaglutide 3 mg151
Oral Semaglutide 7 mg148
Oral Semaglutide 14 mg153
Placebo152
Oral Semaglutide 3 mg23
Oral Semaglutide 7 mg21
Oral Semaglutide 14 mg17
Oral Semaglutide 3 mg168
Oral Semaglutide 7 mg173
Oral Semaglutide 14 mg172
Placebo178
Oral Semaglutide 3 mg15
Oral Semaglutide 7 mg8
Oral Semaglutide 14 mg7
Oral Semaglutide 3 mg161
Oral Semaglutide 14 mg165
Placebo166
Placebo5
Oral Semaglutide 14 mg2
Placebo2
Oral Semaglutide 3 mg184
Oral Semaglutide 7 mg181
Oral Semaglutide 14 mg181
Oral Semaglutide 3 mg172
Placebo172
Oral Semaglutide 3 mg0
Oral Semaglutide 3 mg171
Oral Semaglutide 7 mg170
Oral Semaglutide 14 mg169
Placebo175
Oral Semaglutide 3 mg13
Oral Semaglutide 7 mg10
Oral Semaglutide 14 mg9
Placebo9
Oral Semaglutide 3 mg160
Oral Semaglutide 7 mg160
Placebo164
Oral Semaglutide 3 mg11
Oral Semaglutide 7 mg9
Oral Semaglutide 14 mg8
Placebo8
Oral Semaglutide 3 mg3
Oral Semaglutide 7 mg1
Oral Semaglutide 14 mg3
Oral Semaglutide 3 mg182
Oral Semaglutide 7 mg177
Oral Semaglutide 14 mg180
Placebo184
Oral Semaglutide 3 mg1
Oral Semaglutide 7 mg4
Oral Semaglutide 3 mg173
Oral Semaglutide 7 mg164
Oral Semaglutide 14 mg170
Placebo173
Oral Semaglutide 7 mg6
Oral Semaglutide 3 mg156
Oral Semaglutide 7 mg153
Oral Semaglutide 14 mg159
Placebo162
Oral Semaglutide 3 mg27
Oral Semaglutide 7 mg28
Placebo21
Oral Semaglutide 14 mg0
Placebo1
Oral Semaglutide 3 mg152
Oral Semaglutide 7 mg144
Oral Semaglutide 14 mg151
Placebo155
Oral Semaglutide 3 mg20
Oral Semaglutide 7 mg26
Oral Semaglutide 14 mg18
Placebo18
Oral Semaglutide 3 mg2
Oral Semaglutide 7 mg0
Oral Semaglutide 14 mg1
Placebo0
Oral Semaglutide 3 mg177
Oral Semaglutide 7 mg176
Oral Semaglutide 14 mg176
Placebo177
Oral Semaglutide 3 mg7
Oral Semaglutide 7 mg5
Oral Semaglutide 14 mg5
Oral Semaglutide 7 mg165
Oral Semaglutide 14 mg168
Oral Semaglutide 3 mg8
Placebo6

Participants Who Achieve Body Weight Loss ≥10% (Yes/no)

Participants who achieved weight loss more than or equal to 10% of their baseline body weight (yes/no) at weeks 26 and 52 are presented. The endpoint was evaluated based on data from the in-trial observation period. In trial observation period started at the date of randomisation and included the period after initiation of rescue medication and/or premature trial product discontinuation, if any. Results are based on the data from the in-trial observation period, which started at the date of randomisation and included the period after initiatiion of of rescue medication and/or premature trial product discontinuation, if any. (NCT03021187)
Timeframe: Week 26, week 52

InterventionParticipants (Count of Participants)
Week 2672577393Week 2672577394Week 2672577395Week 2672577392Week 5272577392Week 5272577393Week 5272577395Week 5272577394
YesNo
Oral Semaglutide 3 mg2
Oral Semaglutide 7 mg12
Oral Semaglutide 14 mg19
Placebo1
Oral Semaglutide 3 mg175
Oral Semaglutide 7 mg162
Oral Semaglutide 14 mg154
Placebo176
Oral Semaglutide 3 mg4
Oral Semaglutide 7 mg17
Oral Semaglutide 14 mg21
Oral Semaglutide 3 mg170
Oral Semaglutide 7 mg154
Oral Semaglutide 14 mg149
Placebo172

Participants Who Achieve Body Weight Loss ≥5% (Yes/no)

Participants who achieved weight loss more than or equal to 5% of their baseline body weight (yes/no) at weeks 26 and 52 are presented. The endpoint was evaluated based on data from the in-trial observation period. In trial observation period started at the date of randomisation and included the period after initiation of rescue medication and/or premature trial product discontinuation, if any. (NCT03021187)
Timeframe: Week 26, week 52

InterventionParticipants (Count of Participants)
Week 2672577392Week 2672577393Week 2672577394Week 2672577395Week 5272577395Week 5272577392Week 5272577393Week 5272577394
YesNo
Oral Semaglutide 3 mg23
Oral Semaglutide 7 mg53
Placebo5
Oral Semaglutide 3 mg154
Oral Semaglutide 7 mg121
Oral Semaglutide 14 mg106
Placebo172
Oral Semaglutide 3 mg30
Oral Semaglutide 7 mg48
Oral Semaglutide 14 mg67
Placebo9
Oral Semaglutide 3 mg144
Oral Semaglutide 7 mg123
Oral Semaglutide 14 mg103
Placebo164

Participants Who Achieve HbA1c <7.0 % (53 mmol/Mol) Without Hypoglycaemia (Severe or BG Confirmed Symptomatic Hypoglycaemia) and no Weight Gain (Yes/no)

Participants who achieved HbA1c less than 7.0 % without severe or blood glucose (BG) confirmed symptomatic hypoglycaemia and without weight gain (yes/no) at weeks 26 and 52 are presented. Severe hypoglycaemia was defined as an episode requiring assistance of another person to actively administer carbohydrate or glucagon, or take other corrective actions. BG-confirmed symptomatic hypoglycaemia was defined as an episode with plasma glucose value <3.1 mmol/L with symptoms consistent with hypoglycaemia. Results are based on the data from the in-trial observation period, which was the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of rescue medication and/or premature discontinuation of trial product. (NCT03021187)
Timeframe: Week 26, week 52

InterventionParticipants (Count of Participants)
Week 2672577392Week 2672577394Week 2672577393Week 2672577395Week 5272577392Week 5272577393Week 5272577394Week 5272577395
YesNo
Oral Semaglutide 3 mg32
Oral Semaglutide 7 mg47
Oral Semaglutide 14 mg76
Placebo4
Oral Semaglutide 3 mg144
Oral Semaglutide 7 mg127
Oral Semaglutide 14 mg97
Placebo172
Oral Semaglutide 3 mg27
Oral Semaglutide 7 mg43
Oral Semaglutide 14 mg61
Placebo8
Oral Semaglutide 3 mg146
Oral Semaglutide 7 mg126
Oral Semaglutide 14 mg107
Placebo164

Participants Who Achieve HbA1c Reduction ≥1% (10.9 mmol/Mol) and Weight Loss ≥3% (Yes/no)

Participants who achieved HbA1c reduction more than or equal to 1% of their baseline HbA1c and weight loss of more than or equal to 3% of their baseline body weight (yes/no) at weeks 26 and 52 are presented. Results are based on the data from the in-trial observation period, which was the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of rescue medication and/or premature discontinuation of trial product. (NCT03021187)
Timeframe: Week 26, week 52

InterventionParticipants (Count of Participants)
Week 2672577392Week 2672577395Week 2672577393Week 2672577394Week 5272577395Week 5272577392Week 5272577393Week 5272577394
YesNo
Oral Semaglutide 3 mg28
Oral Semaglutide 7 mg51
Oral Semaglutide 14 mg76
Placebo7
Oral Semaglutide 3 mg148
Oral Semaglutide 7 mg123
Oral Semaglutide 14 mg97
Placebo169
Oral Semaglutide 3 mg20
Oral Semaglutide 7 mg37
Oral Semaglutide 14 mg64
Placebo5
Oral Semaglutide 3 mg153
Oral Semaglutide 7 mg132
Oral Semaglutide 14 mg104
Placebo167

Participants Who Achieve: HbA1c < 7.0% (53 mmol/Mol) (American Diabetes Association (ADA) Target) (Yes/no)

Number of particpants achieving HbA1c < 7.0 % (53 mmol/mol) according to American Diabetes Association (ADA) target, at week 26 and week 52. The endpoint was evaluated based on data from the in-trial observation period. In trial observation period started at the date of randomisation and included the period after initiation of rescue medication and/or premature trial product discontinuation, if any. (NCT03021187)
Timeframe: Week 26, week 52

InterventionParticipants (Count of Participants)
Week 2672577394Week 2672577395Week 2672577392Week 2672577393Week 5272577392Week 5272577393Week 5272577394Week 5272577395
NoYes
Oral Semaglutide 7 mg74
Oral Semaglutide 14 mg101
Placebo12
Oral Semaglutide 3 mg126
Oral Semaglutide 7 mg100
Oral Semaglutide 14 mg72
Placebo164
Oral Semaglutide 3 mg50
Oral Semaglutide 7 mg67
Oral Semaglutide 14 mg91
Placebo16
Oral Semaglutide 3 mg123
Oral Semaglutide 7 mg102
Oral Semaglutide 14 mg77
Placebo156

Participants Who Achieve: HbA1c ≤ 6.5% (48 mmol/Mol) (AACE Target) (Yes/no)

Number of participants achieving HbA1c ≤ 6.5% (48 mmol/mol) according to American Association of Clinical Endocrinologists (AACE) target, at week 26 and week 52. The endpoint was evaluated based on data from the in-trial observation period. In trial observation period started at the date of randomisation and included the period after initiation of rescue medication and/or premature trial product discontinuation, if any. (NCT03021187)
Timeframe: Week 26, week 52

InterventionParticipants (Count of Participants)
Week 2672577393Week 2672577394Week 2672577395Week 2672577392Week 5272577392Week 5272577394Week 5272577395Week 5272577393
YesNo
Oral Semaglutide 3 mg24
Oral Semaglutide 7 mg45
Oral Semaglutide 14 mg74
Placebo6
Oral Semaglutide 3 mg152
Oral Semaglutide 7 mg129
Oral Semaglutide 14 mg99
Placebo170
Oral Semaglutide 3 mg20
Oral Semaglutide 7 mg33
Oral Semaglutide 14 mg65
Placebo4
Oral Semaglutide 3 mg153
Oral Semaglutide 7 mg136
Oral Semaglutide 14 mg103
Placebo168

Percent Change in Muscle Strength

Determine if metformin treatment augments strength gains in conjunction with progressive resistance training by one repetition maximum assessments. Maximum (1RM) leg extension muscle strength was assessed at week 4 (to account for neurological adaptations during the initial stages of the resistance program) and week 16. The percent change from week 4 to week 16 is reported. (NCT02308228)
Timeframe: Week 4 and week 16

InterventionPercent change (Mean)
Metformin15.3
Placebo, Sugar Pill23.1

Percent Change in Normal Density Muscle Size by Computed Tomography

The ability of metformin to improve the hypertrophic response at the whole muscle level will be quantified by computed tomography. Percent change in normal density muscle area will be calculated as the difference between week 16 and week 0. (NCT02308228)
Timeframe: 16 weeks

InterventionPercent change (Mean)
Metformin4.2
Placebo, Sugar Pill10.5

Percent Change in Total Body Lean Mass by DXA

To determine if metformin improves changes in body composition associated with progressive resistance training. Percent change in total body lean mass in kg was calculated as the difference between week 16 and week 0 from a total body DXA scan. (NCT02308228)
Timeframe: 16 weeks

InterventionPercent change (Mean)
Metformin0.41
Placebo, Sugar Pill1.95

Percent Change in Type 2 Myofiber Cross Sectional Area

The ability of metformin to improve the hypertrophic response to resistance training will be determined. Muscle biopsies of the vastus lateralis will be used to quantify myofiber cross-sectional area. The percent change in type 2 myofiber size between week 16 and week 0 was used. (NCT02308228)
Timeframe: 16 weeks

InterventionPercent change (Mean)
Metformin18.5
Placebo, Sugar Pill14.5

Body Weight Change From Baseline

"Body weight change from baseline after 24 weeks.~For open-label groups the descriptive mean is provided, for randomised groups adjusted means are provided. The means are adjusted separately for metformin alone and metformin plus sulphonylurea background medication." (NCT01159600)
Timeframe: Baseline and 24 weeks

Interventionkg (Mean)
Met: Placebo-0.45
Met: Empa 10mg-2.08
Met: Empa 25mg-2.46
Met: Empa 25mg Open Label-1.33
Met+SU: Placebo-0.39
Met+SU: Empa 10mg-2.16
Met+SU: Empa 25mg-2.39
Met+SU: Empa 25mg Open Label-1.29

Confirmed Hypoglycaemic Adverse Events

Number of patients with confirmed hypoglycaemic events, as reported as adverse events. (NCT01159600)
Timeframe: From first intake of randomised trial medication until 7 days after last trial medication intake, up to 231 days

Interventionpercentage of participants (Number)
Met: Placebo0.5
Met: Empa 10mg1.8
Met: Empa 25mg1.4
Met: Empa 25mg Open Label2.9
Met+SU: Placebo8.4
Met+SU: Empa 10mg16.1
Met+SU: Empa 25mg11.5
Met+SU: Empa 25mg Open Label6.9

HbA1c Change From Baseline

"Change from baseline in HbA1c after 24 weeks.~For open-label groups the descriptive mean is provided, for randomised groups adjusted means are provided. The means are adjusted separately for metformin alone and metformin plus sulphonylurea background medication." (NCT01159600)
Timeframe: Baseline and 24 weeks

Interventionpercentage of HbA1c (Mean)
Met: Placebo-0.13
Met: Empa 10mg-0.70
Met: Empa 25mg-0.77
Met: Empa 25mg Open Label-2.78
Met+SU: Placebo-0.17
Met+SU: Empa 10mg-0.82
Met+SU: Empa 25mg-0.77
Met+SU: Empa 25mg Open Label-2.53

Mean Daily Plasma Glucose (MDG) Change From Baseline

"Change from baseline in mean daily glucose (MDG) using the 8-point blood glucose profile, after 24 weeks of treatment.~For open-label groups the descriptive mean is provided, for randomised groups adjusted means are provided. The means are adjusted separately for metformin alone and metformin plus sulphonylurea background medication." (NCT01159600)
Timeframe: Baseline and 24 weeks

Interventionmg/dL (Mean)
Met: Placebo-1.99
Met: Empa 10mg-9.64
Met: Empa 25mg-14.36
Met: Empa 25mg Open Label-35.47
Met+SU: Placebo0.00
Met+SU: Empa 10mg-10.01
Met+SU: Empa 25mg-13.06
Met+SU: Empa 25mg Open Label-29.34

Body Weight (kg) Change From Baseline After 52 Weeks of Treatment

Body Weight (kg) - Change From Baseline After 52 Weeks of Treatment (NCT01289990)
Timeframe: Baseline and 52 weeks

Interventionkg (Least Squares Mean)
BI 10773 Low (Drug Naive)-2.70
BI 10773 High (Drug Naive)-2.61
Placebo (Drug Naive)-0.48
Sitagliptin 100mg (Drug Naive)0.14
BI 10773 Low (Pioglitazone)-1.50
BI 10773 High (Pioglitazone)-1.40
Placebo (Pioglitazone)0.59
BI 10773 Low (Metformin)-2.27
BI 10773 High (Metformin)-2.84
Placebo (Metformin)-0.54
BI 10773 Low (Metformin+Sulfonylurea)-2.28
BI 10773 High (Metformin+Sulfonylurea)-2.32
Placebo (Metformin+Sulfonylurea)-0.31

Body Weight (kg) Change From Baseline After 76 Weeks of Treatment

Body Weight (kg) - Change From Baseline After 76 Weeks of Treatment (NCT01289990)
Timeframe: Baseline and 76 weeks

Interventionkg (Least Squares Mean)
BI 10773 Low (Drug Naive)-2.24
BI 10773 High (Drug Naive)-2.45
Placebo (Drug Naive)-0.43
Sitagliptin 100mg (Drug Naive)0.10
BI 10773 Low (Pioglitazone)-1.47
BI 10773 High (Pioglitazone)-1.21
Placebo (Pioglitazone)0.50
BI 10773 Low (Metformin)-2.39
BI 10773 High (Metformin)-2.65
Placebo (Metformin)-0.46
BI 10773 Low (Metformin+Sulfonylurea)-2.44
BI 10773 High (Metformin+Sulfonylurea)-2.28
Placebo (Metformin+Sulfonylurea)-0.63

Changes From Baseline in Glycosylated Haemoglobin (HbA1c) (%) After 52 Weeks of Treatment

Change from baseline in HbA1c after 52 weeks (NCT01289990)
Timeframe: Baseline and 52 weeks

Intervention% of HbA1c (Least Squares Mean)
BI 10773 Low (Drug Naive)-0.70
BI 10773 High (Drug Naive)-0.82
Placebo (Drug Naive)0.09
Sitagliptin 100mg (Drug Naive)-0.58
BI 10773 Low (Pioglitazone)-0.63
BI 10773 High (Pioglitazone)-0.71
Placebo (Pioglitazone)-0.03
BI 10773 Low (Metformin)-0.69
BI 10773 High (Metformin)-0.76
Placebo (Metformin)-0.07
BI 10773 Low (Metformin+Sulfonylurea)-0.78
BI 10773 High (Metformin+Sulfonylurea)-0.74
Placebo (Metformin+Sulfonylurea)-0.04

Changes From Baseline in HbA1c (%) After 76 Weeks of Treatment

Change from baseline in HbA1c after 76 weeks (NCT01289990)
Timeframe: Baseline and 76 weeks

Intervention% of HbA1c (Least Squares Mean)
BI 10773 Low (Drug Naive)-0.65
BI 10773 High (Drug Naive)-0.76
Placebo (Drug Naive)0.13
Sitagliptin 100mg (Drug Naive)-0.53
BI 10773 Low (Pioglitazone)-0.61
BI 10773 High (Pioglitazone)-0.70
Placebo (Pioglitazone)-0.01
BI 10773 Low (Metformin)-0.62
BI 10773 High (Metformin)-0.74
Placebo (Metformin)-0.01
BI 10773 Low (Metformin+Sulfonylurea)-0.74
BI 10773 High (Metformin+Sulfonylurea)-0.72
Placebo (Metformin+Sulfonylurea)-0.03

Diastolic Blood Pressure: Change From Baseline After 52 Weeks of Treatment

Diastolic blood pressure - change from baseline after 52 weeks of treatment (NCT01289990)
Timeframe: Baseline and 52 weeks

InterventionmmHg (Least Squares Mean)
BI 10773 Low (Drug Naive)-1.3
BI 10773 High (Drug Naive)-1.9
Placebo (Drug Naive)-0.2
Sitagliptin 100mg (Drug Naive)-0.3
BI 10773 Low (Pioglitazone)-1.6
BI 10773 High (Pioglitazone)-2.2
Placebo (Pioglitazone)0.4
BI 10773 Low (Metformin)-2.2
BI 10773 High (Metformin)-2.1
Placebo (Metformin)-0.4
BI 10773 Low (Metformin+Sulfonylurea)-1.7
BI 10773 High (Metformin+Sulfonylurea)-1.6
Placebo (Metformin+Sulfonylurea)-1.0

Diastolic Blood Pressure: Change From Baseline After 76 Weeks of Treatment

Diastolic blood pressure - change from baseline after 76 weeks of treatment (NCT01289990)
Timeframe: Baseline and 76 weeks

InterventionmmHg (Least Squares Mean)
BI 10773 Low (Drug Naive)-1.6
BI 10773 High (Drug Naive)-1.6
Placebo (Drug Naive)-0.6
Sitagliptin 100mg (Drug Naive)-0.1
BI 10773 Low (Pioglitazone)-1.3
BI 10773 High (Pioglitazone)-2.0
Placebo (Pioglitazone)0.2
BI 10773 Low (Metformin)-2.5
BI 10773 High (Metformin)-1.9
Placebo (Metformin)-0.5
BI 10773 Low (Metformin+Sulfonylurea)-2.6
BI 10773 High (Metformin+Sulfonylurea)-2.3
Placebo (Metformin+Sulfonylurea)-1.4

Fasting Plasma Glucose Change From Baseline After 52 Weeks of Treatment

Fasting plasma glucose - change from baseline after 52 weeks of treatment (NCT01289990)
Timeframe: Baseline and 52 weeks

Interventionmg/dL (Least Squares Mean)
BI 10773 Low (Drug Naive)-18.9
BI 10773 High (Drug Naive)-23.9
Placebo (Drug Naive)13.3
Sitagliptin 100mg (Drug Naive)-3.9
BI 10773 Low (Pioglitazone)-16.7
BI 10773 High (Pioglitazone)-20.7
Placebo (Pioglitazone)10.3
BI 10773 Low (Metformin)-16.7
BI 10773 High (Metformin)-19.7
Placebo (Metformin)7.6
BI 10773 Low (Metformin+Sulfonylurea)-18.4
BI 10773 High (Metformin+Sulfonylurea)-19.3
Placebo (Metformin+Sulfonylurea)9.4

Fasting Plasma Glucose Change From Baseline After 76 Weeks of Treatment

Fasting plasma glucose - change from baseline after 76 weeks of treatment (NCT01289990)
Timeframe: Baseline and 76 weeks

Interventionmg/dL (Least Squares Mean)
BI 10773 Low (Drug Naive)-17.2
BI 10773 High (Drug Naive)-20.4
Placebo (Drug Naive)14.4
Sitagliptin 100mg (Drug Naive)-1.8
BI 10773 Low (Pioglitazone)-13.9
BI 10773 High (Pioglitazone)-18.0
Placebo (Pioglitazone)9.4
BI 10773 Low (Metformin)-14.5
BI 10773 High (Metformin)-20.9
Placebo (Metformin)10.5
BI 10773 Low (Metformin+Sulfonylurea)-19.5
BI 10773 High (Metformin+Sulfonylurea)-20.4
Placebo (Metformin+Sulfonylurea)11.4

HbA1c (%) Changes From Baseline After 76 Weeks of Treatment

Change from baseline in HbA1c (%) after 76 weeks using MMRM approach (NCT01289990)
Timeframe: Baseline and 76 weeks

Intervention% of HbA1c (Least Squares Mean)
BI 10773 Low (Drug Naive)-0.70
BI 10773 High (Drug Naive)-0.77
Placebo (Drug Naive)0.13
Sitagliptin 100mg (Drug Naive)-0.48
BI 10773 Low (Pioglitazone)-0.67
BI 10773 High (Pioglitazone)-0.77
Placebo (Pioglitazone)-0.05
BI 10773 Low (Metformin)-0.60
BI 10773 High (Metformin)-0.76
Placebo (Metformin)0.07
BI 10773 Low (Metformin+Sulfonylurea)-0.75
BI 10773 High (Metformin+Sulfonylurea)-0.75
Placebo (Metformin+Sulfonylurea)0.06

Systolic Blood Pressure: Change From Baseline After 52 Weeks of Treatment

Systolic blood pressure - change from baseline after 52 weeks of treatment (NCT01289990)
Timeframe: Baseline and 52 weeks

InterventionmmHg (Least Squares Mean)
BI 10773 Low (Drug Naive)-4.9
BI 10773 High (Drug Naive)-4.5
Placebo (Drug Naive)-1.6
Sitagliptin 100mg (Drug Naive)-0.2
BI 10773 Low (Pioglitazone)-1.8
BI 10773 High (Pioglitazone)-3.3
Placebo (Pioglitazone)0.6
BI 10773 Low (Metformin)-3.6
BI 10773 High (Metformin)-5.2
Placebo (Metformin)-0.7
BI 10773 Low (Metformin+Sulfonylurea)-3.1
BI 10773 High (Metformin+Sulfonylurea)-2.7
Placebo (Metformin+Sulfonylurea)-0.2

Systolic Blood Pressure: Change From Baseline After 76 Weeks of Treatment

Systolic blood pressure - change from baseline after 76 weeks of treatment (NCT01289990)
Timeframe: Baseline and 76 weeks

InterventionmmHg (Least Squares Mean)
BI 10773 Low (Drug Naive)-4.1
BI 10773 High (Drug Naive)-4.2
Placebo (Drug Naive)-0.7
Sitagliptin 100mg (Drug Naive)-0.3
BI 10773 Low (Pioglitazone)-1.7
BI 10773 High (Pioglitazone)-3.4
Placebo (Pioglitazone)0.3
BI 10773 Low (Metformin)-5.2
BI 10773 High (Metformin)-4.5
Placebo (Metformin)-0.8
BI 10773 Low (Metformin+Sulfonylurea)-3.8
BI 10773 High (Metformin+Sulfonylurea)-3.7
Placebo (Metformin+Sulfonylurea)-1.6

Waist Circumference (cm) Change From Baseline After 52 Weeks of Treatment

Waist circumference (cm) - change from baseline after 52 weeks of treatment (NCT01289990)
Timeframe: Baseline and 52 weeks

Interventioncm (Least Squares Mean)
BI 10773 Low (Drug Naive)-2.0
BI 10773 High (Drug Naive)-1.7
Placebo (Drug Naive)0.1
Sitagliptin 100mg (Drug Naive)0.4
BI 10773 Low (Pioglitazone)-1.5
BI 10773 High (Pioglitazone)-1.1
Placebo (Pioglitazone)-0.1
BI 10773 Low (Metformin)-1.5
BI 10773 High (Metformin)-2.0
Placebo (Metformin)-0.4
BI 10773 Low (Metformin+Sulfonylurea)-1.5
BI 10773 High (Metformin+Sulfonylurea)-1.5
Placebo (Metformin+Sulfonylurea)-0.2

Waist Circumference (cm) Change From Baseline After 76 Weeks of Treatment

Waist circumference (cm) - change from baseline after 76 weeks of treatment (NCT01289990)
Timeframe: Baseline and 76 weeks

Interventioncm (Least Squares Mean)
BI 10773 Low (Drug Naive)-1.5
BI 10773 High (Drug Naive)-1.6
Placebo (Drug Naive)0.1
Sitagliptin 100mg (Drug Naive)0.5
BI 10773 Low (Pioglitazone)-1.4
BI 10773 High (Pioglitazone)-0.9
Placebo (Pioglitazone)0.0
BI 10773 Low (Metformin)-1.8
BI 10773 High (Metformin)-1.3
Placebo (Metformin)-0.2
BI 10773 Low (Metformin+Sulfonylurea)-1.6
BI 10773 High (Metformin+Sulfonylurea)-1.4
Placebo (Metformin+Sulfonylurea)-0.3

Ae24 (%) of PF-06882961 on Day 28

Percent of dose recovered in urine as unchanged drug. Ae24% = 100* Ae24/Dose (NCT03538743)
Timeframe: 0 to 24 hours post-dose on Day 28

InterventionPercentage (Geometric Mean)
PF-06882961 15mg BID (Cohort 1)0.05747
PF-06882961 50mg BID (Cohort 2)0.03360
PF-06882961 70mg BID (Cohort 3)0.02942
PF-06882961 120mg BID (Cohort 4)NA
PF-06882961 10mg BID (Cohort 5)0.07483
PF-06882961 120mg BID ST (Cohort 6)0.02607
PF-06882961 200mg QD CR (Cohort 7)0.03652
PF-06882961 120mg QD (Cohort 8)0.04094

Amount of Unchanged Drug Recovered in Urine Over 24 Hours (Ae24) of PF-06882961 on Day 28

Ae was the cumulative amount of drug recovered unchanged in urine during the dosing interval, where the dosing interval was 24 hours. Cumulative amount was calculated as sum of urine drug concentration in sample volume for each collection interval. Sample volume = (urine weight in gram [g]/1.020), where 1.020 g/mL was the approximate specific gravity of urine. (NCT03538743)
Timeframe: 0 to 24 hours post-dose on Day 28

Interventionmicrogram (Geometric Mean)
PF-06882961 15mg BID (Cohort 1)17.25
PF-06882961 50mg BID (Cohort 2)33.60
PF-06882961 70mg BID (Cohort 3)41.16
PF-06882961 120mg BID (Cohort 4)NA
PF-06882961 10mg BID (Cohort 5)14.97
PF-06882961 120mg BID ST (Cohort 6)62.63
PF-06882961 200mg QD CR (Cohort 7)72.98
PF-06882961 120mg QD (Cohort 8)49.09

Number of Participants With Laboratory Abnormalities Without Regard to Baseline Abnormality

Following laboratory parameters were assessed against pre-defined abnormality criteria: hematology (hemoglobin, hematocrit, erythrocytes, reticulocytes, platelets, leukocytes, lymphocytes, neutrophils, basophils, eosinophils, monocytes, activated partial thromboplastin time, prothrombin time [PT], PT/international normalized ratio, reticulocytes); chemistry (indirect bilirubin, direct bilirubin, protein, albumin, blood urea nitrogen, creatinine, creatine kinase, urate, calcium, sodium, potassium, chloride, bicarbonate, urine urobilinogen); urinalysis (pH, urine glucose, urine ketones, urine protein, urine hemoglobin, nitrites, leukocyte esterase, urine erythrocytes, urine leukocytes, urine hyaline casts, urine bilirubin). (NCT03538743)
Timeframe: From baseline to up to 14 days after last dose for a total of approximately 42 days

InterventionParticipants (Count of Participants)
Placebo24
PF-06882961 10mg BID7
PF-06882961 15mg BID8
PF-06882961 50mg BID10
PF-06882961 70mg BID8
PF-06882961 120mg BID8
PF-06882961 120mg BID ST9
PF-06882961 120mg QD7
PF-06882961 200mg QD CR10

Renal Clearance (CLr) of PF-06882961 on Day 28

CLr was calculated as Ae divided by AUCtau, where dosing interval is 24 hours. (NCT03538743)
Timeframe: 0 to 24 hours post-dose on Day 28

InterventionmL/min (Geometric Mean)
PF-06882961 15mg BID (Cohort 1)0.3273
PF-06882961 50mg BID (Cohort 2)0.3385
PF-06882961 70mg BID (Cohort 3)0.3094
PF-06882961 120mg BID (Cohort 4)NA
PF-06882961 10mg BID (Cohort 5)0.5470
PF-06882961 120mg BID ST (Cohort 6)0.2006
PF-06882961 200mg QD CR (Cohort 7)0.2895
PF-06882961 120mg QD (Cohort 8)0.3178

Terminal Half-life (t½) of PF-06882961 on Day 28

Plasma decay half-life is the time measured for the plasma concentration to decrease by one half. (NCT03538743)
Timeframe: 0, 1, 2, 4, 6, 8, 10, 12, 14 and 24 hrs post dose on Day 28

Interventionhours (Mean)
PF-06882961 15mg BID (Cohort 1)5.100
PF-06882961 50mg BID (Cohort 2)5.067
PF-06882961 70mg BID (Cohort 3)4.681
PF-06882961 120mg BID (Cohort 4)6.203
PF-06882961 10mg BID (Cohort 5)8.090
PF-06882961 120mg BID ST (Cohort 6)6.730
PF-06882961 200mg QD CR (Cohort 7)5.773
PF-06882961 120mg QD (Cohort 8)4.954

AUC24 and AUCtau of PF-06882961 on Day 1, Day 14 or 21 and Day 28

Area under the concentration-time profile from time zero to time 24 hours (AUC24) was calculated as AUCtau1 +AUCtau2, where AUCtau was area under the plasma concentration-time profile from time zero to time tau (tau1 = 0 to 10 hours and tau2=10 to 24 hours). AUCtau was determined using linear/log trapezoidal method. (NCT03538743)
Timeframe: 0, 1, 2, 4, 6, 8, 10, 12, 14 and 24 hrs post dose on Day 1, 14 or 21, and 28

,,,,,,,
Interventionnanogram.hours/milliliter (ng.h/mL) (Geometric Mean)
AUC24 on Day 1AUCtau1 on Day 1AUCtau2 on Day 1AUC24 on Day 14 or 21AUCtau1 on Day 14 or 21AUCtau2 on Day 14 or 21AUC24 on Day 28AUCtau1 on Day 28AUCtau2 on Day 28
PF-06882961 10mg BID (Cohort 5)178.774.50103.7201.685.57115.4455.9190.8261.0
PF-06882961 120mg BID (Cohort 4)666.1260.3401.9814937724361836835344852
PF-06882961 120mg BID ST (Cohort 6)324.0147.7176.42660957.31693597322493668
PF-06882961 120mg QD (Cohort 8)184.6NANA1204NANA2723NANA
PF-06882961 15mg BID (Cohort 1)707.5288.1414.8853.8348.6500.1876.7331.1534.7
PF-06882961 200mg QD CR (Cohort 7)393.9NANA1291NANA4372NANA
PF-06882961 50mg BID (Cohort 2)1502741.4678.52092880.311751653671.1960.1
PF-06882961 70mg BID (Cohort 3)645.8279.7364.9298814621517317111531970

Maximum Plasma Concentration (Cmax) of PF-06882961 on Day 1, Day 14 or 21 and Day 28

"For BID dosing, parameters were calculated for both dosing intervals (0-10 hr = interval 1 and 10-24 hr = interval 2) and were displayed as Cmax1, Cmax2.~Cmax1: maximum plasma concentration during the dosing interval τ1 =0 to 10 hours.~Cmax2: maximum plasma concentration during the dosing interval τ2=10 to 24 hours." (NCT03538743)
Timeframe: 0, 1, 2, 4, 6, 8, 10, 12, 14 and 24 hours post dose on Day 1, 14 or 21, and 28

,,,,,,,
Interventionnanogram/milliliter (ng/mL) (Geometric Mean)
Cmax on Day 1Cmax1 on Day 1Cmax2 on Day 1Cmax on Day 14 or 21Cmax1 on Day 14 or 21Cmax2 on Day 14 or 21Cmax on Day 28Cmax1 on Day 28Cmax2 on Day 28
PF-06882961 10mg BID (Cohort 5)15.0212.8213.9818.6315.3117.1638.3830.4235.01
PF-06882961 120mg BID (Cohort 4)51.6136.5144.97788.4682.7505.3685.2649.2617.9
PF-06882961 120mg BID ST (Cohort 6)26.0224.0621.64188.5143.0178.4437.6357.1410.3
PF-06882961 120mg QD (Cohort 8)20.40NANA100.7NANA192.2NANA
PF-06882961 15mg BID (Cohort 1)50.5842.6940.6365.7855.0063.8981.5650.2474.22
PF-06882961 200mg QD CR (Cohort 7)28.67NANA98.11NANA303.9NANA
PF-06882961 50mg BID (Cohort 2)124.4119.168.77149.8130.2127.9133.7103.8117.2
PF-06882961 70mg BID (Cohort 3)49.7545.0142.33253.6235.1202.8328.8197.9306.5

Number of Participants With Abnormal Electrocardiogram (ECG) Interval

"ECG categorical summarization criteria: 1. PR interval (the interval between the start of the P wave and the start of the QRS complex, corresponding to the time between the onset of the atrial depolarization and onset of ventricular depolarization): a) greater than or equal to (>=) 300 millisecond (msec), b) >=25% increase when baseline is > 200 msec or >=50% increase when baseline is less than or equal to (<=) 200 msec.~2. QRS duration (time from ECG Q wave to the end of the S wave corresponding to ventricle depolarization): a) >=140 msec, b) >=50% increase from baseline.~3. QTcF interval (QT corrected using the Fridericia formula): a) >450 msec and <=480 msec, b) >480 msec and <=500 msec, c) >500 msec, d) >30 msec and <=60 msec increase from baseline, e) >60 msec increase from baseline" (NCT03538743)
Timeframe: From baseline to up to 14 days after last dose for a total of approximately 42 days

,,,,,,,,
InterventionParticipants (Count of Participants)
PR interval ≥300 msec%Change in PR interval ≥25/50%QRS duration ≥140 msec%Change in QRS duration ≥50%QTcF interval >450 and ≤480 msecQTcF interval >480 and ≤500 msecQTcF interval >500 msecChange in QTcF interval >30 and ≤60 msecChange in QTcF interval >60 msec
PF-06882961 10mg BID000000010
PF-06882961 120mg BID000000010
PF-06882961 120mg BID ST000000000
PF-06882961 120mg QD000000000
PF-06882961 15mg BID000010000
PF-06882961 200mg QD CR000000000
PF-06882961 50mg BID000000000
PF-06882961 70mg BID000000000
Placebo000020000

Number of Participants With Abnormal Vital Signs

Vital signs categorical summarization criteria: 1) supine systolic blood pressure (SBP) <90 millimeters of mercury (mmHg); 2) supine diastolic blood pressure (DBP) <50 mmHg; 3) supine pulse rate <40 or >120 beats per minute (bpm); 4) change from baseline (increase or decrease) in supine SBP greater than or equal to (>=) 30 mmHg; 5) change from baseline (increase or decrease) in supine DBP >= 20 mmHg. (NCT03538743)
Timeframe: From baseline to up to 14 days after last dose for a total of approximately 42 days

,,,,,,,,
InterventionParticipants (Count of Participants)
Supine SBP <90 mmHgSupine SBP increase >=30 mmHgSupine SBP decrease >=30 mmHgSupine DBP <50 mmHgSupine DBP increase >=20 mmHgSupine DBP decrease >=20 mmHgSupine pulse rate <40 bpmSupine pulse rate >120 bpm
PF-06882961 10mg BID30211200
PF-06882961 120mg BID01301300
PF-06882961 120mg BID ST32322400
PF-06882961 120mg QD02502200
PF-06882961 15mg BID20521100
PF-06882961 200mg QD CR11401300
PF-06882961 50mg BID12310200
PF-06882961 70mg BID33514100
Placebo34911600

Number of Participants With All-causality and Treatment-related Treatment-emergent Adverse Events (TEAEs)

Treatment-related adverse event (AE) was any untoward medical occurrence attributed to study treatment in a participant who received study treatment. A serious AE (SAE) was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; life-threatening; initial or prolonged inpatient hospitalization; persistent or significant disability/incapacity; congenital anomaly/birth defect. Any such events with initial onset or increasing in severity after the first dose of study treatment were counted as treatment-emergent. (NCT03538743)
Timeframe: From baseline to up to 35 days after last dose for a total of approximately 63 days

,,,,,,,,
InterventionParticipants (Count of Participants)
All-causality AEAll-causality SAETreatment-related AETreatment-related SAE
PF-06882961 10mg BID6040
PF-06882961 120mg BID8080
PF-06882961 120mg BID ST9190
PF-06882961 120mg QD8080
PF-06882961 15mg BID8040
PF-06882961 200mg QD CR9090
PF-06882961 50mg BID100100
PF-06882961 70mg BID8070
Placebo170140

Time for Cmax (Tmax) of PF-06882961 on Day 1, Day 14 or 21 and Day 28

Time for Cmax, Cmax1 and Cmax2 (Tmax, Tmax1 and Tmax2) of PF-06293620 was observed directly from data as time of first occurrence. (NCT03538743)
Timeframe: 0, 1, 2, 4, 6, 8, 10, 12, 14 and 24 hrs post dose on Day 1, 14 or 21, and 28

,,,,,,,
Interventionhours (Median)
Tmax on Day 1Tmax1 on Day 1Tmax2 on Day 1Tmax on Day 14 or 21Tmax1 on Day 14 or 21Tmax2 on Day 14 or 21Tmax on Day 28Tmax1 on Day 28Tmax2 on Day 28
PF-06882961 10mg BID (Cohort 5)NA2.0012.0NA6.0012.0NA4.0012.0
PF-06882961 120mg BID (Cohort 4)NA4.0014.0NA1.5412.0NA4.0012.0
PF-06882961 120mg BID ST (Cohort 6)NA2.0014.0NA6.0014.0NA6.0012.0
PF-06882961 120mg QD (Cohort 8)3.00NANA6.00NANA10.0NANA
PF-06882961 15mg BID (Cohort 1)NA4.0014.0NA4.0013.0NA5.0012.0
PF-06882961 200mg QD CR (Cohort 7)13.0NANA12.0NANA14.0NANA
PF-06882961 50mg BID (Cohort 2)NA4.0014.0NA4.0013.0NA3.0012.0
PF-06882961 70mg BID (Cohort 3)NA2.0014.0NA1.0512.0NA6.0012.0

Change From Baseline to 28 Weeks in Body Weight

LS means of the body weight change from baseline to primary endpoint at week 28 was adjusted by treatment, country, metformin use, week, treatment-by-week interaction, and baseline body weight as covariate, via a MMRM analysis. (NCT02152371)
Timeframe: Baseline, 28 Weeks

Interventionkilogram(kg) (Least Squares Mean)
Dulaglutide + Insulin Glargine-1.91
Placebo + Insulin Glargine0.50

Change From Baseline to 28 Weeks in Daily Mean Insulin Glargine Dose

Least Square (LS) Means of the insulin dose change from baseline to primary endpoint at week 28 was adjusted by treatment, country, metformin use, week, treatment-by-week interaction, and baseline insulin dose as covariate, via a MMRM analysis. (NCT02152371)
Timeframe: Baseline, 28 Weeks

Interventionunits (u) (Least Squares Mean)
Dulaglutide + Insulin Glargine12.75
Placebo + Insulin Glargine25.94

Change From Baseline to 28 Weeks in Fasting Serum Glucose (FSG)

FSG is a test to determine glucose levels after an overnight fast. LS means FSG change from baseline to primary endpoint at week 28 was calculated using a mixed effects model for repeated measures (MMRM) analysis adjusted by treatment, country, metformin use, week, treatment-by-week interaction, and baseline FSG as covariate. (NCT02152371)
Timeframe: Baseline, 28 Weeks

Interventionmilligram per deciliter (mg/dL) (Least Squares Mean)
Dulaglutide + Insulin Glargine-44.63
Placebo + Insulin Glargine-27.90

Change From Baseline to 28 Weeks in Hemoglobin A1c (HbA1c)

HbA1c is a form of hemoglobin that is measured primarily to identify the average plasma glucose concentration over prolonged periods of time. Least-squares (LS) mean and standard error (SE) changes from baseline in HbA1c at 28 weeks were measured using mixed model regression and restricted maximum likelihood (REML) with treatment, pooled country, visit, and treatment-by -visit interaction as fixed effects, baseline as covariate, and participant as a random effect. (NCT02152371)
Timeframe: Baseline, 28 Weeks

Interventionpercentage of change (Least Squares Mean)
Dulaglutide + Insulin Glargine-1.44
Placebo + Insulin Glargine-0.67

Number of Participants With Adjudicated Acute Pancreatitis Events

The number of cases of acute pancreatitis confirmed by adjudication. A summary of serious and other non-serious AEs, regardless of causality, is located in the Reported Adverse Events module. (NCT02152371)
Timeframe: Baseline through 28 Weeks

Interventionparticipants (Number)
Dulaglutide + Insulin Glargine0
Placebo + Insulin Glargine0

Number of Participants With Dulaglutide Anti-Drug Antibodies

Dulaglutide anti-drug antibodies (ADA) were assessed at baseline, Weeks 12 and 28. A participant was considered to have treatment-emergent (TE) dulaglutide ADAs if the participant had at least 1 titer that was TE relative to baseline, defined as a 4-fold or greater increase in titer from baseline measurement. (NCT02152371)
Timeframe: Baseline, Week 12 and Week 28

Interventionparticipants (Number)
Dulaglutide + Insulin Glargine0
Placebo + Insulin Glargine2

Number of Participants With Investigator Reported and Adjudicated Cardiovascular Events

Cardiovascular (CV) adverse events (AEs) were adjudicated by an independent committee of physicians with cardiology expertise external to the sponsor. Deaths occurring during the study treatment period and nonfatal CV AEs were to be adjudicated. Nonfatal CV events that were to be adjudicated were myocardial infarction; hospitalization for unstable angina; hospitalization for heart failure; coronary interventions (such as coronary artery bypass graft (CABG) or percutaneous coronary intervention (PCI); and cerebrovascular events, including cerebrovascular accident (CVA/stroke), and transient ischemic attack (TIA). (NCT02152371)
Timeframe: Baseline through 28 Weeks

Interventionparticipants (Number)
Dulaglutide + Insulin Glargine3
Placebo + Insulin Glargine1

Number of Participants With Thyroid Tumors/Neoplasms (Including C-Cell Hyperplasia)

(NCT02152371)
Timeframe: Baseline through 28 Weeks

Interventionparticipants (Number)
Dulaglutide + Insulin Glargine1
Placebo + Insulin Glargine0

Percentage of Participants Achieving HbA1c Target of <7.0% and Without Weight Gain (<0.1 kg)

(NCT02152371)
Timeframe: 28 Weeks

Interventionpercentage of participants (Number)
Dulaglutide + Insulin Glargine52.7
Placebo + Insulin Glargine20.0

Percentage of Participants Achieving HbA1c Target of <7.0% and Without Weight Gain (<0.1 Kilograms [kg]) at 28 Weeks and Without Documented Symptomatic Hypoglycemia During the Maintenance Period (Weeks 12-28)

Percentage of participants who achieved a target HbA1c target of <7%, without weight gain and without documented symptomatic hypoglycemia at 28 weeks were analyzed using regression model, controlling for treatment, pre-treatment, baseline HbA1c and country. (NCT02152371)
Timeframe: 28 Weeks

Interventionpercentage of participants (Number)
Dulaglutide + Insulin Glargine40.7
Placebo + Insulin Glargine16.7

Percentage of Participants Achieving HbA1c Target of <7.0% at 28 Weeks and Without Documented Symptomatic Hypoglycemia During the Maintenance Period (Weeks 12-28)

Percentage of participants achieving target HbA1c of <7.0% at 28 weeks without documented symptomatic hypoglycemia are presented. Documented symptomatic hypoglycemia is defined as any time a participant experienced symptoms and or signs associated with hypoglycemia and had a plasma glucose of <=70 mg/dL. (NCT02152371)
Timeframe: 28 Weeks

Interventionpercentage of participants (Number)
Dulaglutide + Insulin Glargine52.0
Placebo + Insulin Glargine28.0

Percentage of Participants Discontinuing the Study Due to Severe, Persistent Hyperglycemia

(NCT02152371)
Timeframe: Baseline through 28 Weeks

Interventionpercentage of participants (Number)
Dulaglutide + Insulin Glargine0
Placebo + Insulin Glargine0

Rate of Hypoglycemic Events up to 28 Weeks

The rate of total hypoglycemic events any type per 30 days is presented. The hypoglycemia rate per 30 days during defined period is calculated by the number of hypoglycemia events within the period/number of days participant at risk within the period*30 days. (NCT02152371)
Timeframe: Baseline through 28 Weeks

Interventionrate of hypoglycemic events per 30 days (Mean)
Dulaglutide + Insulin Glargine0.63
Placebo + Insulin Glargine0.70

Change From Baseline to 28 Weeks in 7-Point Self Monitored Plasma Glucose (SMPG)

The LS means of the 7-point SMPG change from baseline to primary endpoint at week 28 was measured using a MMRM analysis adjusted by treatment, country, metformin use, week, treatment-by-week interaction, and baseline SMPG as covariate. (NCT02152371)
Timeframe: Baseline, 28 Weeks

,
Interventionmg/dL (Least Squares Mean)
Pre-Morning Meal (n=133,129)Morning Meal 2-Hour Postprandial (n=123,119)Pre-Midday Meal (n=133,127)Midday Meal 2-Hour Post Prandial (n=123,117)Pre-Evening Meal (n=133,129)Evening Meal 2-Hour Postprandial (n=126,122)3:00 AM (Morning) (n=124,117)
Dulaglutide + Insulin Glargine-44.03-64.16-40.89-51.13-43.68-48.63-39.77
Placebo + Insulin Glargine-35.97-46.97-25.34-32.98-28.71-27.35-20.30

Percentage of Participants Achieving HbA1c Targets of <7.0% or ≤6.5%

Percentage of participants who achieved HbA1c levels of <7% or ≤6.5% were analyzed using a logistic regression model, controlling for treatment, pre-treatment, baseline HbA1c and country. (NCT02152371)
Timeframe: 28 Weeks

,
Interventionpercentage of participants (Number)
HbA1c <= 6.5HbA1c < 7.0
Dulaglutide + Insulin Glargine50.769.3
Placebo + Insulin Glargine16.735.3

Percentage of Participants With Self-Reported Events of Hypoglycemia

Hypoglycemic events (HE) were classified as severe (defined as episodes requiring the assistance of another person to actively administer resuscitative actions), documented symptomatic (defined as any time a participant feels that he/she is experiencing symptoms and/or signs associated with hypoglycemia, and has a plasma glucose level of =<3.9 mmol/L), asymptomatic (defined as events not accompanied by typical symptoms of hypoglycemia but with a measured plasma glucose of =<3.9 mmol/L), nocturnal (defined as any hypoglycemic event that occurred between bedtime and waking), or probable symptomatic (defined as events during which symptoms of hypoglycemia were not accompanied by a plasma glucose determination). The percentage of participants with self-reported hypoglycemic events is presented. (NCT02152371)
Timeframe: Baseline through 28 Weeks

,
Interventionpercentage of participants (Number)
SymptomaticAsymptomaticSevereNocturnalProbable Symptomatic
Dulaglutide + Insulin Glargine35.342.70.728.02.7
Placebo + Insulin Glargine30.039.30.028.72.0

Adjusted Mean Change From Baseline in 2-hour Post Prandial Glucose (PPG) From a Liquid Meal Tolerance Test (MTT) at Week 24 (Last Observation Carried Forward [LOCF])

Baseline was defined as the last assessment on or prior to the date of the first dose of the double-blind study medication. PPG measurements were obtained at week 24 in the doubleblind period, including observations prior to rescue. (NCT01606007)
Timeframe: Baseline (Week 0) and at Week 24

InterventionMG/DL PPG (Mean)
Arm 1: Saxagliptin+Metformin XR+Placebo-35.6
Arm 2: Dapagliflozin+Metformin XR+Placebo-70.4
Arm 3: Saxagliptin+Dapagliflozin+Metformin XR-79.6

Adjusted Mean Change From Baseline in Body Weight at Week 24

Baseline was defined as the last assessment on or prior to the date of the first dose of the double-blind study medication. Body weight measurements were obtained at Week 24 in the doubleblind period, including observations prior to rescue. (NCT01606007)
Timeframe: Baseline (Week 0) and at Week 24

InterventionBody weight Kg (Mean)
Arm 1: Saxagliptin+Metformin XR+Placebo0.00
Arm 2: Dapagliflozin+Metformin XR+Placebo-2.39
Arm 3: Saxagliptin+Dapagliflozin+Metformin XR-2.05

Adjusted Mean Change From Baseline in Fasting Plasma Glucose (FPG) at Week 24

Baseline was defined as the last assessment on or prior to the date of the first dose of the double-blind study medication. FPG measurements were obtained at Week 24 in the doubleblind period, including observations prior to rescue. (NCT01606007)
Timeframe: Baseline (Week 0) and at Week 24

Interventionmg/dL (Mean)
Arm 1: Saxagliptin+Metformin XR+Placebo-14.0
Arm 2: Dapagliflozin+Metformin XR+Placebo-31.7
Arm 3: Saxagliptin+Dapagliflozin+Metformin XR-37.8

Adjusted Mean Change From Baseline in Hemoglobin A1C (HbA1c) at Week 24

HbA1c was measured as percent of hemoglobin by a central laboratory. Baseline was defined as the last assessment on or prior to the date of the first dose of the double-blind study medication. HbA1c measurements were obtained at Week 24 in the double-blind period, including observations prior to rescue. (NCT01606007)
Timeframe: Baseline (Week 0) and at Week 24

Intervention% HbA1c (Mean)
Arm 1: Saxagliptin+Metformin XR+Placebo-0.88
Arm 2: Dapagliflozin+Metformin XR+Placebo-1.20
Arm 3: Saxagliptin+Dapagliflozin+Metformin XR-1.47

Adjusted Percentage of Participants Achieving a Therapeutic Glycemic Response (Hemoglobin A1c [HbA1C]) <7.0% at Week 24 (Last Observation Carried Forward [LOCF])

Therapeutic glycemic response is defined as HbA1c <7.0%. Data after rescue medication was excluded from this analysis. HbA1c was measured as a percent of hemoglobin. (NCT01606007)
Timeframe: At Week 24

Intervention% of Participants (Number)
Arm 1: Saxagliptin+Metformin XR+Placebo18.3
Arm 2: Dapagliflozin+Metformin XR+Placebo22.2
Arm 3: Saxagliptin+Dapagliflozin+Metformin XR41.4

Change in Blood Lipids (Cholesterol)

Lipid levels such as cholesterol will be examined by standard blood chemistry (NCT02546609)
Timeframe: Baseline, Day 112

Interventionmg/dL (Mean)
Placebo-0.8
Leu Met Sil 0.5mg-20.5
Leu Met Sil 1.0mg-5.9

Change in Blood Lipids (High Density Lipoprotein:HDL)

Lipid levels such as HDL will be examined by standard blood chemistry (NCT02546609)
Timeframe: Baseline, Day 112

Interventionmg/dL (Mean)
Placebo-1.0
Leu Met Sil 0.5mg-13.3
Leu Met Sil 1.0mg1.2

Change in C-reactive Protein

CRP levels will be examined by standard blood chemistry (NCT02546609)
Timeframe: Baseline, Day 112

Interventionmg/L (Geometric Mean)
Placebo1.02
Leu Met Sil 0.5mg1.27
Leu Met Sil 1.0mg1.08

Change in Circulating Cytokeratin 18 Fragments (M30)

Change in Circulating Cytokeratin 18 Fragments (M30) from Baseline to Week 16 will be examined through standard blood chemistry (NCT02546609)
Timeframe: Baseline, Day 112

InterventionU/L (Mean)
Placebo70.685
Leu Met Sil 0.5mg55.386
Leu Met Sil 1.0mg37.847

Change in Fasting Glucose

Fasting glucose will be examined through standard fasting blood chemistry (NCT02546609)
Timeframe: Baseline, Day 112

Interventionmg/dL (Mean)
Placebo0.8
Leu Met Sil 0.5mg-2.7
Leu Met Sil 1.0mg-6.3

Change in Heamoglobin A1c (HbA1c)

HbA1c will be examined through standard blood chemistry (NCT02546609)
Timeframe: Baseline, Day 112

Interventionpercentage (Mean)
Placebo0.07
Leu Met Sil 0.5mg-0.15
Leu Met Sil 1.0mg-0.11

Change in Hepatic Fat

To evaluate the change in hepatic fat content assessed by proton-density-fat-fraction (PDFF) employing magnetic resonance imaging (MRI). (NCT02546609)
Timeframe: Baseline, Day 112

Interventionpercentage (Mean)
Placebo-10.046
Leu Met Sil 0.5mg3.083
Leu Met Sil 1.0mg-4.013

Change in Insulin

Insulin levels will be examined through standard blood chemistry (NCT02546609)
Timeframe: Baseline, Day 112

InterventionμIU/mL (Mean)
Placebo-8.30
Leu Met Sil 0.5mg-6.60
Leu Met Sil 1.0mg-5.30

Change in Insulin Sensitivity (HOMA-IR)

HOMA-IR levels will be examined by standard blood chemistry (NCT02546609)
Timeframe: Baseline, Day 112

InterventionmU/L (Geometric Mean)
Placebo0.89
Leu Met Sil 0.5mg0.80
Leu Met Sil 1.0mg0.85

Change in Low Density Lipoproteins (LDL)

Lipid levels such as LDL will be examined by standard blood chemistry (NCT02546609)
Timeframe: Baseline, Day 112

Interventionmg/dL (Mean)
Placebo-1.0
Leu Met Sil 0.5mg-13.3
Leu Met Sil 1.0mg1.2

Change in Serum AlanineAaminotransferase (ALT) Levels

Serum AlanineAminotransferase (ALT) will be examined through standard blood chemistry (NCT02546609)
Timeframe: Baseline, Day 112

InterventionU/L (Mean)
Placebo-4.1
Leu Met Sil 0.5mg1.8
Leu Met Sil 1.0mg-2.7

Change in Triglycerides

Lipid levels such as triglycerides will be examined by standard blood chemistry (NCT02546609)
Timeframe: Baseline, Day 112

Interventionmg/dL (Geometric Mean)
Placebo1.0
Leu Met Sil 0.5mg0.8
Leu Met Sil 1.0mg0.9

ACPRg

First phase response from the hyperglycemic clamp (NCT01779362)
Timeframe: 3-months after a medication washout

Interventionnmol/L (Geometric Mean)
Metformin Alone1.68
Glargine Followed by Metformin1.68
Placebo1.68
Liraglutide + Metformin1.68

Insulin Sensitivity, M/I

Clamp measure of insulin sensitivity (NCT01779362)
Timeframe: 3-months after a medication washout

Interventionx 10-5 mmol/kg/min per pmol/L (Geometric Mean)
Metformin Alone3.53
Glargine Followed by Metformin3.38
Placebo3.63
Liraglutide + Metformin3.49

ß-cell Function Measured by Hyperglycemic Clamp Techniques at M12

Participants had 12-months of active therapy. Secondary results at the end of active intervention. (NCT01779362)
Timeframe: Secondary analysis was on all participants with a Month 12 visit.

,,,
Interventionnmol/L (Geometric Mean)
ACRPgSteady State C-peptideACRPmax
Glargine Followed by Metformin1.8811.614.1
Liraglutide + Metformin2.6821.210.1
Metformin Alone1.9311.713.4
Placebo1.6910.813.6

ß-cell Response Measured by Hyperglycemic Clamp

Clamp measures of ß-cell response, co-primary outcomes (NCT01779362)
Timeframe: 3-months after medication washout (Month 15)

,,,
Interventionnmol/L (Geometric Mean)
Steady State C-peptideACPRmax
Glargine Followed by Metformin3.584.32
Liraglutide + Metformin3.734.58
Metformin Alone3.654.61
Placebo3.604.45

"Number of Subjects Having the Adverse Event Incorrect Dose Administered"

"Number of subjects having the adverse event incorrect dose administered within the system organ class Injury, poisoning and procedural complications" (NCT00909480)
Timeframe: Weeks 0-26

InterventionSubjects (Number)
IDet12
IGlar24

Change in Body Weight From Baseline

(NCT00909480)
Timeframe: Week 0, Week 26

Interventionkg (Mean)
IDet-0.49
IGlar1

Change in HbA1c From Baseline

(NCT00909480)
Timeframe: Week 0, Week 26

Interventionpercentage point change (Mean)
IDet-0.48
IGlar-0.74

Fasting Plasma Glucose (FPG)

(NCT00909480)
Timeframe: Week 26

Interventionmmol/L (Mean)
IDet6.22
IGlar6.09

Glycaemic Control as Measured by Plasma Glucose (9-point Self-measured Profiles)

Plasma glucose measured: before breakfast, 2 hours after breakfast, before lunch, 2 hours after lunch, before dinner, 2 hours after dinner, bedtime and at 3 am. (NCT00909480)
Timeframe: Week 26

,
Interventionmmol/L (Mean)
Before breakfast (N=200, N=197)2 hours after breakfast (N=192, N=188)Before Lunch (N=193, N=189)2 hours After Lunch (N=194, N=186)Before Dinner (N=194, N=186)2 hours after dinner (N=192, N=190)Bedtime (N=190, N=183)At 3AM (N=193, N=186)Before Breakfast Next Day (N=197, N=195)
IDet5.89.17.29.78.210.39.56.65.7
IGlar5.98.76.68.87.59.896.35.6

Hypoglycaemic Episodes, Diurnal

Number of hypoglycaemic episodes from Week 0 to Week 26, defined as major, minor, or symptoms only. Major if unable to treat her/himself. Minor if able to treat her/himself and plasma glucose below 3.1 mmol/L. Symptoms only if able to treat her/himself and no plasma glucose measurement or plasma glucose higher than or equal to 3.1 mmol/L. (NCT00909480)
Timeframe: Weeks 0-26

,
Interventionepisodes (Number)
MajorMinorSymptoms only
IDet075128
IGlar2118222

Hypoglycaemic Episodes, Nocturnal

Number of hypoglycaemic episodes from Week 0 to Week 26, defined as major, minor, or symptoms only. Major if unable to treat her/himself. Minor if able to treat her/himself and plasma glucose below 3.1 mmol/L. Symptoms only if able to treat her/himself and no plasma glucose measurement or plasma glucose higher than or equal to 3.1 mmol/L. (NCT00909480)
Timeframe: Weeks 0-26

,
Interventionepisodes (Number)
MajorMinorSymptoms only
IDet03976
IGlar03061

Hypoglycemic Episodes, Unclassifiable

Number of hypoglycaemic episodes from Week 0 to Week 26, defined as major, minor, or symptoms only. Major if unable to treat her/himself. Minor if able to treat her/himself and plasma glucose below 3.1 mmol/L. Symptoms only if able to treat her/himself and no plasma glucose measurement or plasma glucose higher than or equal to 3.1 mmol/L. (NCT00909480)
Timeframe: Weeks 0-26

,
Interventionepisodes (Number)
MajorMinorSymptoms only
IDet056
IGlar0816

Incidence of Hypoglycaemic Episodes During the Trial

Number of hypoglycaemic episodes from Week 0 to Week 26, defined as major, minor, or symptoms only. Major if unable to treat her/himself. Minor if able to treat her/himself and plasma glucose below 3.1 mmol/L. Symptoms only if able to treat her/himself and no plasma glucose measurement or plasma glucose higher than or equal to 3.1 mmol/L. (NCT00909480)
Timeframe: Weeks 0-26

,
Interventionepisodes (Number)
All EventsMajorMinorSymptoms only
IDet3290119210
IGlar4572156299

Percentage of Subjects Achieving HbA1c Less Than or Equal to 6.5%

The percentage of subjects - overall and by previous OAD treatment - meeting the HbA1c of 6.5% or less (NCT00909480)
Timeframe: Week 26

,
Interventionpercentage (%) of subjects (Number)
Metformin monotherapyMetformin+TZDMetformin+2nd OAD other than TZDAll
IDet2213511
IGlar30131721

Percentage of Subjects Achieving HbA1c Less Than or Equal to 7.0%

The percentage of subjects - overall and by previous OAD treatment - meeting the HbA1c less than or equal to 7% (NCT00909480)
Timeframe: Week 26

,
Interventionpercentage of subjects (Number)
Metformin monotherapyMetformin+TZDMetformin+2nd OAD other than TZDAll
IDet55403138
IGlar70404753

Percentage of Subjects Achieving HbA1c of 6.5% or Less With no Hypoglycaemia

The subjects must have reached target and not have experienced any confirmed symptomatic hypoglycaemia or any confirmed major hypoglycaemia within the last 30 days of treatment. (NCT00909480)
Timeframe: Week 26

,
Interventionpercentage (%) of subjects (Number)
Metformin monotherapyMetformin+TZDMetformin+2nd OAD other than TZDAll
IDet22739
IGlar21131315

Percentage of Subjects Achieving HbA1c of 7% or Less With no Hypoglycaemia

The subjects must have reached target and not have experienced any confirmed symptomatic hypoglycaemia or any confirmed major hypoglycaemia within the last 30 days of treatment. (NCT00909480)
Timeframe: Week 26

,
Interventionpercentage (%) of subjects (Number)
Metformin monotherapyMetformin+TZDMetformin+2nd OAD other than TZDAll
IDet48332532
IGlar52333338

Within-subject Variation of Self Measured Plasma Glucose (SMPG) Before Breakfast

The median values of the sample standard variation (the within subject variation) within the IDet and IGlar arms were plotted against time. (NCT00909480)
Timeframe: Week 26

,
Interventionmmol/L (Median)
Metformin MonotherapyMetformin+TZDMetformin+2nd OAD other than TZDOverall
IDet0.480.720.60.57
IGlar0.670.840.710.71

Mean Change From Baseline at Week 16 (95% Confidence Interval) in Adiponectin - Full Analysis Set

Baseline was defined as value obtained on Day 1 (first day of treatment). Adiponectin was measured in milligrams/liter (mg/L) and values obtained through a central laboratory; normal range was 1.20 to 20.00 mg/L. (NCT00778622)
Timeframe: Baseline to Week 16

Interventionmg/L (Mean)
Glucophage XR in Normal Weight Participants1.742
Glucophage XR in Overweight Participants1.102
Glucophage XR in Obese Participants0.050

Mean Change From Baseline at Week 16 (95% Confidence Interval) in C-Reactive Protein (CRP) - Full Analysis Set

Baseline was defined as value obtained on Day 1 (first day of treatment). C-Reactive Protein (CRP) was measured in milligrams/liter (mg/L) and values were obtained through a central laboratory; normal was less than 5.0 mg/L. (NCT00778622)
Timeframe: Baseline to Week 16

Interventionmg/L (Mean)
Glucophage XR in Normal Weight Participants-0.589
Glucophage XR in Overweight Participants3.144
Glucophage XR in Obese Participants1.633

Mean Change From Baseline at Week 16 (95% Confidence Interval) in Fasting High-density Lipoprotein Cholesterol (HDL-C) - Full Analysis Set

Baseline was defined as value obtained on Day 1 (first day of treatment). High-density lipoprotein cholesterol (HDL-C) was measured in millimoles per liter (mmol/L) and obtained through local laboratories. (NCT00778622)
Timeframe: Baseline to Week 16

Interventionmmol/L (Mean)
Glucophage XR in Normal Weight Participants0.056
Glucophage XR in Overweight Participants0.024
Glucophage XR in Obese Participants0.032

Mean Change From Baseline at Week 16 (95% Confidence Interval) in Fasting Low-density Lipoprotein Cholesterol (LDL-C) - Full Analysis Set

Baseline was defined as values obtained on Day 1. Low-density lipoprotein cholesterol (LDL-C) was measured in millimoles per liter (mmol/L) and obtained through local laboratories. (NCT00778622)
Timeframe: Baseline to Week 16

Interventionmmol/L (Mean)
Glucophage XR in Normal Weight Participants-0.306
Glucophage XR in Overweight Participants-0.143
Glucophage XR in Obese Participants-0.181

Mean Change From Baseline at Week 16 (95% Confidence Interval) in Fasting Total Cholesterol (TC) - Full Analysis Set

For fasting total cholesterol (TC), baseline is defined as Day 1 (first day of treatment). Total cholesterol was measured in millimoles per liter (mmol/L) and obtained through local laboratories. (NCT00778622)
Timeframe: Baseline to Week 16

Interventionmmol/L (Mean)
Glucophage XR in Normal Weight Participants-0.388
Glucophage XR in Overweight Participants-0.048
Glucophage XR in Obese Participants-0.144

Mean Change From Baseline at Week 16 (95% Confidence Interval) in Fasting Triglycerides (TG) - Full Analysis Set

Baseline was defined as value obtained on Day 1 (first day of treatment). Triglycerides (TG) were measured in millimoles per liter (mmol/L)and values obtained through local laboratories. (NCT00778622)
Timeframe: Baseline to Week 16

Interventionmmol/L (Mean)
Glucophage XR in Normal Weight Participants-0.172
Glucophage XR in Overweight Participants0.262
Glucophage XR in Obese Participants-0.041

Mean Change From Baseline at Week 16 (95% Confidence Interval) in Glycosated Hemoglobin A1c (HbA1c) (Last Observation Carried Forward) - Full Analysis Set (FAS)

Baseline for HbA1c is defined as that value obtained at screening visit. HbA1c was measured as a percent (%) of hemoglobin; normal range was 4.7 to 6.4% and values were obtained through a central laboratory. The Last Observation Carried Forward (LOCF) data set includes data recorded at a given visit or, if no observation is recorded at that visit, data carried forward from the previous visit. (NCT00778622)
Timeframe: Baseline to Week 16

Interventionpercentage of hemoglobin (Mean)
Glucophage XR in Normal Weight Participants-1.95
Glucophage XR in Overweight Participants-1.79
Glucophage XR in Obese Participants-1.68

Mean Change From Baseline at Week 16 (95% Confidence Interval) in Plasminogen Activator Inhibitor-1 (PAI-1) - Full Analysis Set

Baseline was defined as value obtained on Day 1 (first day of treatment). PAI-1 (activity) was measured in units/milliliter (U/mL)and values obtained through a central laboratory; normal was less than 25.00 U/mL. (NCT00778622)
Timeframe: Baseline to Week 16

InterventionU/mL (Mean)
Glucophage XR in Normal Weight Participants0.465
Glucophage XR in Overweight Participants1.177
Glucophage XR in Obese Participants-1.792

Mean Change From Baseline at Week 16 (95% Confidence Interval) of Fasting Plasma Glucose (FPG) - Full Analysis Set

Baseline was defined as the value obtained at the screening visit. FPG was measured in millimoles/Liter (mmol/L) and obtained through local laboratories. (NCT00778622)
Timeframe: Baseline to Week 16

Interventionmmol/L (Mean)
Glucophage XR in Normal Weight Participants-1.979
Glucophage XR in Overweight Participants-2.171
Glucophage XR in Obese Participants-2.141

Mean Change From Baseline at Week at Week 16 in ECG Parameter Heart Rate (HR) - Safety Population

Baseline was defined as ECG obtained at the screening visit. ECG was 12-lead. Heart rate (HR) was measured in beats per minute (beats/min). Safety population included participants who enrolled in the study and took at least 1 dose of Glucophage XR. (NCT00778622)
Timeframe: Baseline to Week 16

Interventionbeats/min (Mean)
Glucophage XR in Normal Weight Participants0.4
Glucophage XR in Overweight Participants1.2
Glucophage XR in Obese Participants1.1

Number of Participants Who Had a Normal Electrocardiogram (ECG) at Baseline and an ECG at Week 16 (or Termination Visit) Which Was Considered to be Abnormal With Clinical Significance - Safety Population

Baseline was defined as ECG obtained at the screening visit. A judgment of clinical significance was at the discretion of the investigator. Safety population included participants who enrolled in the study and took at least 1 dose of Glucophage XR. (NCT00778622)
Timeframe: Baseline to Week 16

Interventionparticipants (Number)
Glucophage XR in Normal Weight Participants0
Glucophage XR in Overweight Participants1
Glucophage XR in Obese Participants3

Number of Participants With Clinically Significant Changes From Baseline at Week 16 in the Hematology Laboratory Test Profile - Safety Population

Hematology profile = hematocrit, hemoglobin, red blood cell count (RBC), white blood cell count(WBC), lymphocytes, monocytes, basophils, eosinophils, neutrophils, platelet count. Baseline: value obtained at screening or last value obtained before treatment. LLN=lower limit of normal; ULN=upper limit of normal; preRX=pretreatment. Hemoglobin (g/dL): >3 g/dL decrease from preRX; hematocrit (%): <0.75*preRX; RBC (*10^6 c/uL): <0.75*preRX; platelet count (*10^9 c/uL): <0.67*LLN or >1.5*ULN, of if preRX1.25*ULN, or if preRX ULN, or if preRX>ULN, use >1.2*preRX or 0.750*10^3 c/uL; basophils (*10^3 c/uL): if value >400/mm^3; monocytes (*10^3 c/uL): if value >2000/mm^3; lymphocytes (*10^3 c/uL): if value <0.750*10^3 c/uL or if value >7.50*10^3 c/uL. (NCT00778622)
Timeframe: Baseline to Week 16

Interventionparticipants (Number)
Glucophage XR in Normal Weight Participants0
Glucophage XR in Overweight Participants0
Glucophage XR in Obese Participants0

Number of Participants With Clinically Significant Changes From Baseline at Week 16 in Urinalysis - Safety Population

Urinalysis included pH and specific gravity. Baseline defined as values obtained at screening visit. Clinically significant: outside the reference range (low/high)and judged to be significant by the investigator: Specific gravity 1.003 - 1.035; ph 5 - 8. Safety population included participants who enrolled in the study and took at least 1 dose of Glucophage XR. (NCT00778622)
Timeframe: Baseline to Week 16

Interventionparticipants (Number)
Glucophage XR in Normal Weight Participants0
Glucophage XR in Overweight Participants0
Glucophage XR in Obese Participants0

Mean Change From Baseline at Week 16 in Diastolic and Systolic Blood Pressure - Safety Population

Baseline was defined as the value obtained at screening or value obtained on Day 1 before treatment. Diastolic and systolic blood pressure was measured in millimeters of mercury (mm Hg). Safety population included participants who enrolled in the study and took at least 1 dose of Glucophage XR. (NCT00778622)
Timeframe: Baseline to Week 16

,,
Interventionmm Hg (Mean)
Week 16 change in diastolic blood pressureWeek 16 change in systolic blood pressure
Glucophage XR in Normal Weight Participants-2.2-4.6
Glucophage XR in Obese Participants-1.4-1.7
Glucophage XR in Overweight Participants-4.1-5.5

Number of Participants Who Had Abnormal Increase From Baseline at Week 16 in Kidney or Liver Function Serum Chemistry Values - Safety Population

Baseline defined as value obtained either in screening visit or last value obtained before glucophage XR treatment given on Day 1. Serum chemistries evaluating kidney or liver function: blood urea nitrogen(BUN), serum creatinine (SCr), Alanine aminotransferase (ALT), Aspartate aminotransferase (AST), total bilirubin (BR), uric acid (UA). Abnormal increase in kidney and liver function tests defined as 1.25 - less than, equal to (<=)2.6 times (x) upper limit of normal (ULN)in ALT, AST, total BR, UA; abnormal increase defined as 1.25 to <= 5.1 x ULN in BUN. Safety population included participants who enrolled in the study and took at least 1 dose of Glucophage XR. (NCT00778622)
Timeframe: Baseline to Week 16

,,
Interventionparticipants (Number)
Number with Week 16 ALT 1.25 to <= 2.6xULNNumber with Week 16 ALT > 2.6 x ULNNumber with Week 16 AST 1.25 to <= 2.6xULNNumber with Week 16 AST > 2.6 x ULNNumber with Week 16 Total BR 1.25 to <=2.6xULNNumber with Week 16 Total BR > 2.6 x ULNNumber with Week 16 BUN1.25 to <=5.1xULNNumber with Week 16 BUN > 5.1 x ULNNumber with Week 16 UA 1.25 to <=2.6xULNNumber with Week 16 UA > 2.6 x ULNNumber with Week 16 SCr 1.25 to <=2.6xULNNumber with Week 16 SCr > 1.25 x ULN
Glucophage XR in Normal Weight Participants200030003000
Glucophage XR in Obese Participants904010007000
Glucophage XR in Overweight Participants1105020105000

Number of Participants With Episodes of Lactic Acidosis or Hypoglycemia From Day 1 to Week 16 - Safety Population

Day 1 was first day of treatment. Lactic acidosis defined as elevated blood lactate levels (>5 mmol/L), decreased blood pH, electrolyte disturbances with an increased anion gap, and increased lactate/pyruvate ratio. Hypoglycemia (low levels of blood glucose) was reported as an adverse event. Safety population included participants who had enrolled in the study and took at least 1 dose of glucophage extended release (glucophage XR). If a subject experienced more than one adverse event, the subject was counted once at the highest severity. (NCT00778622)
Timeframe: Day 1 to Week 16

,,
Interventionparticipants (Number)
Lactic AcidosisHypoglycemia
Glucophage XR in Normal Weight Participants01
Glucophage XR in Obese Participants00
Glucophage XR in Overweight Participants00

Adjusted Mean Change in Body Weight

To examine whether treatment with dapagliflozin in combination with insulin is superior in reducing body weight or causing less weight gain as compared to placebo added to insulin treatment after 24 weeks of treatment (LOCF), excluding data after insulin up-titration. (NCT00673231)
Timeframe: Baseline to Week 24

Interventionkg (Least Squares Mean)
Placebo0.02
Dapagliflozin 2.5mg-0.98
Dapagliflozin 5mg-0.98
Dapagliflozin 10mg-1.67

Adjusted Mean Change in Calculated Mean Daily Insulin Dose

To examine whether treatment with dapagliflozin in combination with insulin leads to a lower absolute calculated mean daily insulin dose as compared to placebo added to insulin treatment alone, from baseline to week 24, including data after insulin up-titration. (NCT00673231)
Timeframe: Baseline to Week 24

InterventionIU/day (Least Squares Mean)
Placebo5.08
Dapagliflozin 2.5mg-1.80
Dapagliflozin 5mg-0.61
Dapagliflozin 10mg-1.16

Adjusted Mean Change in Fasting Plasma Glucose (FPG)

To examine whether treatment with dapagliflozin in combination with insulin is superior in reducing Fasting Plasma Glucose (FPG) as compared to placebo added to insulin treatment after 24 weeks of treatment, excluding data after insulin up-titration. (NCT00673231)
Timeframe: Baseline to Week 24

Interventionmg/dL (Least Squares Mean)
Placebo3.3
Dapagliflozin 2.5mg-12.5
Dapagliflozin 5mg-18.8
Dapagliflozin 10mg-21.7

Adjusted Mean Change in HbA1c Levels

To assess the efficacy of 2.5 mg, 5 mg and 10 mg dapagliflozin compared to placebo as add-on therapy to insulin in improving glycaemic control in participants with type 2 diabetes who have inadequate glycaemic control on ≥ 30 IU injectable insulin daily for at least 8 weeks prior to enrolment, as determined by the change in HbA1c levels from baseline to Week 24, excluding data after insulin up-titration. (NCT00673231)
Timeframe: Baseline to Week 24

InterventionPercent (Least Squares Mean)
Placebo-0.30
Dapagliflozin 2.5mg-0.75
Dapagliflozin 5mg-0.82
Dapagliflozin 10mg-0.90

Proportion of Participants With Calculated Mean Daily Insulin Dose Reduction

To examine whether treatment with dapagliflozin in combination with insulin leads to higher percentage of participants with calculated mean daily insulin dose reduction from baseline to week 24 (i.e. reduction >= 10%) as compared to placebo added to insulin treatment. (NCT00673231)
Timeframe: Baseline to Week 24

InterventionPercentage of participants (Least Squares Mean)
Placebo11.0
Dapagliflozin 2.5mg18.1
Dapagliflozin 5mg16.8
Dapagliflozin 10mg19.7

Proportion of Participants With Lack of Glycemic Control

Participants with lack of glycemic control or insulin up-titration for failing to achieve pre-specified glycemic targets (NCT00673231)
Timeframe: Baseline to Week 24

InterventionParticipants (Number)
Placebo54
Dapagliflozin 2.5mg22
Dapagliflozin 5mg24
Dapagliflozin 10mg19

Adjusted Mean Change in Body Weight

To assess the effect of dapagliflozin plus metformin compared to glipizide plus metformin on body weight after 52 weeks double-blind treatment. (NCT00660907)
Timeframe: Baseline to Week 52

Interventionkg (Least Squares Mean)
Dapagliflozin Plus Metformin-3.22
Glipizide Plus Metformin1.44

Adjusted Mean Change in HbA1c Levels

To assess the effect of dapagliflozin plus metformin compared to glipizide plus metformin on the absolute change from baseline in HbA1c level after 52 weeks double-blind treatment in patients with type 2 diabetes who have inadequate glycaemic control on 1500 mg/day or higher doses of metformin therapy alone. (NCT00660907)
Timeframe: Baseline to Week 52

Interventionpercent (Least Squares Mean)
Dapagliflozin Plus Metformin-0.52
Glipizide Plus Metformin-0.52

Proportion of Participants With at Least One Episode of Hypoglycemia

To assess the effect of dapagliflozin plus metformin treatment compared to glipizide plus metformin on the occurrence of hypoglycemic events. Least Squares Mean represents the percent of participants adjusted for HbA1c baseline value. (NCT00660907)
Timeframe: Baseline to Week 52

InterventionPercentage of participants (Least Squares Mean)
Dapagliflozin Plus Metformin3.5
Glipizide Plus Metformin40.8

Proportion of Participants With Body Weight Reduction of at Least 5%

To evaluate the effect of dapagliflozin plus metformin compared to glipizide plus metformin on body weight assessed by a reduction after 52 weeks of at least 5% compared to baseline. Least Squares Mean represents the percent of participants adjusted for baseline value. (NCT00660907)
Timeframe: Baseline to Week 52

InterventionPercentage of participants (Least Squares Mean)
Dapagliflozin Plus Metformin33.3
Glipizide Plus Metformin2.5

Change in Kidney Function

Estimated glomerular filtration rate (eGFR) will be calculated from serum creatinine measurements at baseline and after 3, 6, 9 and 12 months. Change from baseline at 12 months is reported. (NCT02903511)
Timeframe: 12 months

InterventionmL/min/1.73 m^2 (Mean)
Metformin-0.41
Placebo-3.35

Change in Total Kidney Volume

Total kidney volume will be measured by MRI (magnetic resonance imaging) at baseline and at 12 months. Percentage change from baseline in height-adjusted total kidney volume is reported. (NCT02903511)
Timeframe: 12 months

Interventionpercent change (Mean)
Metformin3.45
Placebo3.15

Rate of Serious Adverse Events (SAE)

Serious adverse events occurring from the time of signing informed consent until the end of the study will be monitored in both treatment arms (NCT02903511)
Timeframe: 12 months

InterventionParticipants (Count of Participants)
Metformin2
Placebo0

Safety and Tolerability of Metformin

Percentage of participants who at the end of 12 months are still prescribed the full randomized dose of metformin or placebo, and the percentage of participants who are prescribed at least 50% of the randomized dose (NCT02903511)
Timeframe: 12 months

,
Interventionpercentage of participants (Number)
Full Dose50% Dose
Metformin5082
Placebo100100

Mean Change in HbA1c (ITT)

Mean change in HbA1c through Week 12 (NCT00943917)
Timeframe: Day 0 to Week 12

Interventionpercent change (Mean)
ITCA 650 20 mcg/Day - STAGE I-.93
ITCA 650 40 mcg/Day - STAGE I-0.96
Exenatide Injection - STAGE I-0.75

Mean Change in HbA1c (ITT)

Mean change in HbA1c through Week 24 (NCT00943917)
Timeframe: Day 0 to Week 24

Interventionpercent change (Mean)
ITCA 650 20/20-0.89
ITCA 650 20/60-1.26
ITCA 650 40/40-0.70
ITCA 650 40/80-1.36
Ex Inj/ITCA 650 40-1.01
Ex Inj/ITCA 650 60-1.51

Mean Change in HbA1c (ITT)

Mean change in HbA1c through Week 48 (NCT00943917)
Timeframe: Day 0 to Week 48

Interventionpercent change (Mean)
ITCA 650 20/20-1.13
ITCA 650 20/60-1.25
ITCA 650 40/40-0.48
ITCA 650 40/80-1.40
Ex Inj/ITCA 650 40-1.16
Ex Inj/ITCA 650 60-1.84

Mean Change in HbA1c (Per Protocol)

Mean change in HbA1c over first 12 weeks (Stage I) (NCT00943917)
Timeframe: Day 0 and Week 12

Interventionpercent change (Mean)
ITCA 650 20 mcg/Day - STAGE I-0.96
ITCA 650 40 mcg/Day - STAGE I-1.04
Exenatide Injection - STAGE I-0.82

Mean Change in HbA1c (Per Protocol)

Mean change in HbA1c through Week 24 (NCT00943917)
Timeframe: Day 0 to Week 24

Interventionpercent change (Mean)
ITCA 650 20/20-.89
ITCA 650 20/60-1.26
ITCA 650 40/40-0.67
ITCA 650 40/80-1.36
Ex Inj/ITCA 650 40-1.01
Ex Inj/ITCA 650 60-1.51

Mean Change in HbA1c (Per Protocol)

Mean change in HbA1c through Week 48 (NCT00943917)
Timeframe: Day 0 to Week 48

Interventionpercent change (Mean)
ITCA 650 20/20-1.00
ITCA 650 20/60-1.23
ITCA 650 40/40-0.69
ITCA 650 40/80-1.37
Ex Inj/ITCA 650 40-1.45
Ex Inj/ITCA 650 60-1.88

Development of Diabetes.

Primary outcome for years 2002-2008 defined according to American Diabetes Association criteria (fasting plasma glucose level >= 126 mg/dL [7.0 mmol/L] or 2-hour plasma glucose >= 200 mg/dL [11.1 mmol/L], after a 75 gram oral glucose tolerance test (OGTT), and confirmed with a repeat test). (NCT00038727)
Timeframe: Outcomes were assessed from 1996-2008 (approximately 12 years including 6 years of DPP).

Interventiondiabetes incidence (cases per 100 person (Number)
1 Original Lifestyle5.3
2 Original Metformin6.4
3 Original Placebo7.8

Mortality

All cause-mortality through clinic reports and National Death Index search (NCT00038727)
Timeframe: Outcomes were assessed throughout follow-up from 1996 to 2022. National Death Index search conducted in 2019 using early release data as of Dec 2018.

InterventionParticipants (Count of Participants)
1 Original Lifestyle158
2 Original Metformin152
3 Original Placebo143

Prevalence of Aggregate Microvascular Complication

Aggregate microvascular disease is defined as the average prevalence of 3 components: (1) retinopathy measured by photography (ETDRS of 20 or greater); (2) neuropathy detected by Semmes Weinstein 10 gram monofilament, and (3) nephropathy based on estimated glomerular filtration rate (eGFR by chronic kidney disease (CKD-Epi) equation ) (<45 ml/min, confirmed) and albumin-to-creatinine ratio in spot urine (> 30mg/gm, confirmed). (NCT00038727)
Timeframe: Outcomes were assessed from 2012-2013 (approximately 2 years).

Interventionaverage percentage of participants (Number)
1 Original Lifestyle11.3
2 Original Metformin13
3 Original Placebo12.4

Subclinical Atherosclerosis

Measured using coronary artery calcification (CAC). (NCT00038727)
Timeframe: Outcomes were assessed from 2012-2013 (approximately 2 years).

,,
InterventionCAC geometric mean in AU (Geometric Mean)
MenWomen
1 Original Lifestyle70.16.0
2 Original Metformin40.26.1
3 Original Placebo63.75.3

Change in 2-hour Post-prandial Glucose From Baseline to Week 26

The table below shows the least-squares (LS) mean change in 2-hour post-prandial glucose from Baseline to Week 26 for each treatment group. The statistical analyses show the treatment differences (ie, each canagliflozin or sitagliptin group minus placebo) in the LS mean change. (NCT01106677)
Timeframe: Day 1 (Baseline) and Week 26

Interventionmg/dL (Least Squares Mean)
Placebo/Sitagliptin-9.79
Canagliflozin 100 mg-47.9
Canagliflozin 300 mg-57.1
Sitagliptin 100 mg-49.3

Change in Fasting Plasma Glucose (FPG) From Baseline to Week 26

The table below shows the least-squares (LS) mean change in FPG from Baseline to Week 26 for each treatment group. The statistical analyses show the treatment differences (ie, each canagliflozin or sitagliptin group minus placebo) in the LS mean change. (NCT01106677)
Timeframe: Day 1 (Baseline) and Week 26

Interventionmg/dL (Least Squares Mean)
Placebo/Sitagliptin2.47
Canagliflozin 100 mg-27.3
Canagliflozin 300 mg-37.8
Sitagliptin 100 mg-20.2

Change in Fasting Plasma Glucose (FPG) From Baseline to Week 52

The table below shows the least-squares (LS) mean change in FPG from Baseline to Week 52 for each active treatment group. The statistical analyses show the treatment differences (ie, each canagliflozin group minus sitagliptin) in the LS mean change. (NCT01106677)
Timeframe: Day 1 (Baseline) and Week 52

Interventionmg/dL (Least Squares Mean)
Canagliflozin 100 mg-26.2
Canagliflozin 300 mg-35.2
Sitagliptin 100 mg-17.7

Change in HbA1c From Baseline to Week 26

The table below shows the least-squares (LS) mean change in HbA1c from Baseline to Week 26 for each treatment group. The statistical analyses show the treatment differences (ie, each canagliflozin or sitagliptin group minus placebo) in the LS mean change. (NCT01106677)
Timeframe: Day 1 (Baseline) and Week 26

InterventionPercent (Least Squares Mean)
Placebo/Sitagliptin-0.17
Canagliflozin 100 mg-0.79
Canagliflozin 300 mg-0.94
Sitagliptin 100 mg-0.82

Change in HbA1c From Baseline to Week 52

The table below shows the least-squares (LS) mean change in HbA1c from Baseline to Week 52 for each active treatment group. The statistical analyses show the treatment differences (ie, each canagliflozin group minus sitagliptin) in the LS mean change. (NCT01106677)
Timeframe: Day 1 (Baseline) and Week 52

InterventionPercent (Least Squares Mean)
Canagliflozin 100 mg-0.73
Canagliflozin 300 mg-0.88
Sitagliptin 100 mg-0.73

Change in Systolic Blood Pressure (SBP) From Baseline to Week 26

The table below shows the least-squares (LS) mean change in SBP from Baseline to Week 26 for each treatment group. The statistical analyses show the treatment differences (ie, each canagliflozin or sitagliptin group minus placebo) in the LS mean change. (NCT01106677)
Timeframe: Day 1 (Baseline) and Week 26

InterventionmmHg (Least Squares Mean)
Placebo/Sitagliptin1.52
Canagliflozin 100 mg-3.84
Canagliflozin 300 mg-5.06
Sitagliptin 100 mg-1.83

Change in Systolic Blood Pressure (SBP) From Baseline to Week 52

The table below shows the least-squares (LS) mean change in SBP from Baseline to Week 52 for each active treatment group. The statistical analyses show the treatment differences (ie, each canagliflozin group minus sitagliptin) in the LS mean change. (NCT01106677)
Timeframe: Day 1 (Baseline) and Week 52

InterventionmmHg (Least Squares Mean)
Canagliflozin 100 mg-3.53
Canagliflozin 300 mg-4.65
Sitagliptin 100 mg-0.66

Percent Change in Body Weight From Baseline to Week 26

The table below shows the least-squares (LS) mean percent change in body weight from Baseline to Week 26 for each treatment group. The statistical analyses show the treatment differences (ie, each canagliflozin or sitagliptin group minus placebo) in the LS mean percent change. (NCT01106677)
Timeframe: Day 1 (Baseline) and Week 26

InterventionPercent change (Least Squares Mean)
Placebo/Sitagliptin-1.2
Canagliflozin 100 mg-3.7
Canagliflozin 300 mg-4.2
Sitagliptin 100 mg-1.2

Percent Change in Body Weight From Baseline to Week 52

The table below shows the least-squares (LS) mean percent change in body weight from Baseline to Week 52 for each active treatment group. The statistical analyses show the treatment differences (ie, each canagliflozin group minus sitagliptin) in the LS mean percent change. (NCT01106677)
Timeframe: Day 1 (Baseline) and Week 52

InterventionPercent change (Least Squares Mean)
Canagliflozin 100 mg-3.8
Canagliflozin 300 mg-4.2
Sitagliptin 100 mg-1.3

Percent Change in High-density Lipoprotein Cholesterol (HDL-C) From Baseline to Week 26

The table below shows the least-squares (LS) mean percent change in HDL-C from Baseline to Week 26 for each treatment group. The statistical analyses show the treatment differences (ie, each canagliflozin or sitagliptin group minus placebo) in the LS mean percent change. (NCT01106677)
Timeframe: Day 1 (Baseline) and Week 26

InterventionPercent change (Least Squares Mean)
Placebo/Sitagliptin3.7
Canagliflozin 100 mg10.4
Canagliflozin 300 mg12.1
Sitagliptin 100 mg5.0

Percent Change in High-density Lipoprotein Cholesterol (HDL-C) From Baseline to Week 52

The table below shows the least-squares (LS) mean percent change in HDL-C from Baseline to Week 52 for each active treatment group. The statistical analyses show the treatment differences (ie, each canagliflozin group minus sitagliptin) in the LS mean percent change. (NCT01106677)
Timeframe: Day 1 (Baseline) and Week 52

InterventionPercent change (Least Squares Mean)
Canagliflozin 100 mg11.2
Canagliflozin 300 mg13.3
Sitagliptin 100 mg6.0

Percent Change in Triglycerides From Baseline to Week 26

The table below shows the least-squares (LS) mean percent change in triglycerides from Baseline to Week 26 for each treatment group. The statistical analyses show the treatment differences (ie, each canagliflozin or sitagliptin group minus placebo) in the LS mean percent change. (NCT01106677)
Timeframe: Day 1 (Baseline) and Week 26

InterventionPercent change (Least Squares Mean)
Placebo/Sitagliptin3.2
Canagliflozin 100 mg1.6
Canagliflozin 300 mg-1.4
Sitagliptin 100 mg1.0

Percent Change in Triglycerides From Baseline to Week 52

The table below shows the least-squares (LS) mean percent change in triglycerides from Baseline to Week 52 for each active treatment group. The statistical analyses show the treatment differences (ie, each canagliflozin group minus sitagliptin) in the LS mean percent change. (NCT01106677)
Timeframe: Day 1 (Baseline) and Week 52

InterventionPercent change (Least Squares Mean)
Canagliflozin 100 mg1.9
Canagliflozin 300 mg2.7
Sitagliptin 100 mg-0.4

Percentage of Patients With HbA1c <7% at Week 26

The table below shows the percentage of patients with HbA1c <7% at Week 26 in each treatment group. The statistical analyses show the treatment differences between each canagliflozin or sitagliptin group and placebo. (NCT01106677)
Timeframe: Week 26

InterventionPercentage of patients (Number)
Placebo/Sitagliptin29.8
Canagliflozin 100 mg45.5
Canagliflozin 300 mg57.8
Sitagliptin 100 mg54.5

Adjusted Mean Change in 2-hour Post Liquid Meal Glucose Rise

To compare the change in 2-hour post liquid meal glucose rise achieved with dapagliflozin versus placebo from baseline to week 24. (NCT00984867)
Timeframe: Baseline to Week 24

Interventionmg/dL (Least Squares Mean)
Placebo-6.84
Dapagliflozin-21.65

Adjusted Mean Change in Body Weight

To compare the change in total body weight achieved with dapagliflozin versus placebo from baseline to week 24. (NCT00984867)
Timeframe: Baseline to Week 24

Interventionkg (Least Squares Mean)
Placebo-0.26
Dapagliflozin-2.14

Adjusted Mean Change in Fasting Plasma Glucose (FPG)

To compare the change in FPG achieved with dapagliflozin versus placebo from baseline to week 24. (NCT00984867)
Timeframe: Baseline to Week 24

Interventionmg/dL (Least Squares Mean)
Placebo3.81
Dapagliflozin-24.11

Adjusted Mean Change in HbA1c in Participants With Baseline HbA1c ≥8%

To compare the change in HbA1c in participants with baseline HbA1c ≥8% achieved with dapagliflozin versus placebo from baseline to week 24. (NCT00984867)
Timeframe: Baseline to Week 24

InterventionPercent (Least Squares Mean)
Placebo0.03
Dapagliflozin-0.80

Adjusted Mean Change in HbA1c Levels

To compare the change from baseline in HbA1c after 24 weeks treatment (LOCF) between dapagliflozin and placebo in patients with type 2 diabetes who are inadequately controlled on sitagliptin alone or on sitagliptin plus metformin. (NCT00984867)
Timeframe: Baseline to Week 24

InterventionPercent (Least Squares Mean)
Placebo0.04
Dapagliflozin-0.45

Adjusted Mean Change in Seated Systolic Blood Pressure (SBP) in Participants With Baseline SBP>=130 mmHg

To compare the change in seated systolic blood pressure (SBP) in participants with baseline seated SBP >=130 achieved with dapagliflozin versus placebo from baseline to week 8. (NCT00984867)
Timeframe: Baseline to Week 8

InterventionmmHg (Least Squares Mean)
Placebo-5.12
Dapagliflozin-5.98

Proportion of Participants Achieving a Therapeutic Glycemic Response Defined as a Reduction in HbA1c of ≥0.7% Compared to Baseline

To compare the proportion of participants achieving a therapeutic glycaemic response, defined as a reduction in HbA1c of ≥0.7% compared to baseline, with dapagliflozin versus placebo at week 24. Least Squares Mean represents the percent of participants adjusted for HbA1c baseline value. (NCT00984867)
Timeframe: Baseline to Week 24

InterventionPercentage of participants (Least Squares Mean)
Placebo16.6
Dapagliflozin35.3

Change From Baseline in Glycosylated Hemoglobin (HbA1c) at Week 26

The change from Baseline to Week 26 in HbA1c (the concentration of glucose bound to hemoglobin as a percent of the absolute maximum that can be bound). (NCT01023581)
Timeframe: Baseline and Week 26.

Interventionpercentage glycosylated hemoglobin (Least Squares Mean)
Placebo0.15
Alogliptin 25 QD-0.52
Alogliptin 12.5 BID-0.56
Metformin 500 BID-0.65
Metformin 1000 BID-1.11
Alogliptin 12.5 BID + Metformin 500 BID-1.22
Alogliptin 12.5 BID + Metformin 1000 BID-1.55

Change From Baseline in Fasting Plasma Glucose Over Time

The change from Baseline in fasting plasma glucose was assessed at Weeks 1, 2, 4, 8, 12, 16, 20 and 26. Least Squares Means were from an ANCOVA model with treatment and geographic region as fixed effects, and baseline fasting plasma glucose as a covariate. (NCT01023581)
Timeframe: Baseline and Weeks 1, 2, 4, 8, 12, 16, 20 and 26.

,,,,,,
Interventionmg/dL (Least Squares Mean)
Week 1 (n=102, 103, 94, 95, 104, 101, 109)Week 2 (n=105, 112, 105, 102, 108, 106, 111)Week 4 (n=105, 112, 106, 106, 110, 106, 111)Week 8 (n=105, 112, 106, 106, 110, 106, 112)Week 12 (n=105, 112, 106, 106, 110, 106, 112)Week 16 (n=105, 112, 106, 106, 110, 106, 112)Week 20 (n=105, 112, 106, 106, 110, 106, 112)Week 26 (n=105, 112, 106, 106, 110, 106, 112)
Alogliptin 12.5 BID-11.9-11.6-16.6-12.1-14.7-14.7-12.3-9.7
Alogliptin 12.5 BID + Metformin 1000 BID-36.3-43.6-44.1-43.8-44.7-47.7-44.6-45.9
Alogliptin 12.5 BID + Metformin 500 BID-32.7-34.5-37.6-32.9-31.6-35.9-33.8-31.7
Alogliptin 25 QD-3.9-7.4-11.5-10.9-9.7-7.1-9.2-6.1
Metformin 1000 BID-23.1-22.2-29.0-30.7-30.7-33.5-35.1-31.9
Metformin 500 BID-12.6-14.5-16.9-11.8-14.0-13.3-10.9-11.5
Placebo5.74.67.27.111.610.18.712.4

Change From Baseline in HbA1c Over Time

"The change from Baseline in HbA1c (the concentration of glucose bound to hemoglobin as a percent of the absolute maximum that can be bound) was assessed at Weeks 4, 8, 12, 16 and 20.~Least squares means are from an analysis of covariance (ANCOVA) model with treatment and geographic region as fixed effects, and baseline HbA1c as a covariate." (NCT01023581)
Timeframe: Baseline and Weeks 4, 8, 12, 16, and 20.

,,,,,,
Interventionpercentage glycosylated hemoglobin (Least Squares Mean)
Week 4 (n=95, 97, 89, 94, 102, 94, 101)Week 8 (n=102, 104, 104, 103, 108, 102, 111)Week 12 (n=102, 104, 104, 103, 108, 102, 111)Week 16 (n=102, 104, 104, 103, 108, 102, 111)Week 20 (n=102, 104, 104, 103, 108, 102, 111)
Alogliptin 12.5 BID-0.42-0.58-0.62-0.63-0.59
Alogliptin 12.5 BID + Metformin 1000 BID-0.75-1.17-1.40-1.50-1.54
Alogliptin 12.5 BID + Metformin 500 BID-0.70-1.08-1.22-1.26-1.25
Alogliptin 25 QD-0.34-0.51-0.53-0.58-0.57
Metformin 1000 BID-0.58-0.86-1.02-1.09-1.14
Metformin 500 BID-0.37-0.59-0.68-0.72-0.68
Placebo0.090.080.120.130.12

Alanine Aminotransferase (ALT) at Week 12.

The ALT hepatic transaminase levels are going to be measured at week 12 with standardized techniques. (NCT02113241)
Timeframe: Week 12.

InterventionU/L (Mean)
Dapagliflozin32.1
Placebo38.1

Aspartate Aminotransferase (AST) at Week 12.

The hepatic transaminase AST will be evaluated with standardized methods at week 12 (NCT02113241)
Timeframe: Week 12

InterventionU/L (Mean)
Dapagliflozin31.1
Placebo29.5

AUC of Glucose at Week 12.

The AUC of glucose will be calculated from the glucose values obtained from the minuted oral glucose tolerance curve at week 12 (NCT02113241)
Timeframe: Week 12

Interventionmmol*hr/L (Mean)
Dapagliflozin1153
Placebo1129

AUC of Insulin at Week 12.

The AUC will be calculated from the insulin values obtained from the minuted oral glucose tolerance curve at week 12 (NCT02113241)
Timeframe: Week 12

Interventionpmol*h/L (Mean)
Dapagliflozin45016
Placebo119704

Body Mass Index at Week 12

The Body Mass index it's going to be calculated at week 12 with the Quetelet index. (NCT02113241)
Timeframe: Week 12

Interventionkg/m^2 (Mean)
Dapagliflozin32.6
Placebo32.1

Body Weight at Week 12.

The weight it's going to be measured at week 12 with a bioimpedance balance. (NCT02113241)
Timeframe: Week 12

Interventionkilograms (Mean)
Dapagliflozin81.2
Placebo79.6

Creatinine at Week 12.

The creatinine levels are going to be measured at week 12 with standardized techniques. (NCT02113241)
Timeframe: Week 12.

Interventionmmol/L (Mean)
Dapagliflozin0.07
Placebo0.05

Diastolic Blood Pressure at Week 12.

The diastolic blood pressure is going to be evaluated at week 12 with a digital sphygmomanometer. (NCT02113241)
Timeframe: Week 12

InterventionmmHg (Mean)
Dapagliflozin76
Placebo79

Fat Mass at Week 12.

The fat mass is going to be evaluated at week 12 through bioimpedance. (NCT02113241)
Timeframe: Week 12

Interventionkilograms (Mean)
Dapagliflozin32.7
Placebo34.4

Glucose at Minute 120 at Week 12.

The glucose at minute 120 is going to be evaluated at week 12 during a minuted oral glucose tolerance curve (NCT02113241)
Timeframe: Week 12

Interventionmmol/L (Mean)
Dapagliflozin8.5
Placebo8.8

Glucose at Minute 30 at Week 12.

The glucose at minute 30 is going to be evaluated at week 12 during a minuted oral glucose tolerance curve (NCT02113241)
Timeframe: Week 12

Interventionmmol/L (Mean)
Dapagliflozin10.5
Placebo10.0

Glucose at Minute 60 at Week 12.

The glucose at minute 60 is going to be evaluated at week 12 during a minuted oral glucose tolerance curve (NCT02113241)
Timeframe: Week 12

Interventionmmol/L (Mean)
Dapagliflozin11.1
Placebo11.4

Glucose at Minute 90 at Week 12.

The glucose at minute 90 is going to be evaluated at week 12 during a minuted oral glucose tolerance curve (NCT02113241)
Timeframe: Week 12

Interventionmmol/L (Mean)
Dapagliflozin9.8
Placebo9.9

Glucose Levels at Minute 0 at Week 12.

The fasting glucose (0') levels are going to be evaluated at week 12 with enzymatic/colorimetric techniques. (NCT02113241)
Timeframe: Week 12

Interventionmmol/L (Mean)
Dapagliflozin5.7
Placebo5.8

High Density Lipoprotein (c-HDL) Levels at Week 12.

The c-HDL levels are going to be evaluated at week 12 with enzymatic/colorimetric techniques. (NCT02113241)
Timeframe: Week 12

Interventionmmol/L (Mean)
Dapagliflozin1.3
Placebo1.3

Insulinogenic Index (Total Insulin Secretion) at Week 12.

"The insulinogenic index is a ratio that relates enhancement of circulating insulin to the magnitude of the corresponding glycemic stimulus.~Total insulin secretion was calculated with the insulinogenic index (ΔAUC insulin/ΔAUC glucose), the entered values reflect the total insulin secretion at week 12." (NCT02113241)
Timeframe: Week 12

Interventionindex (Mean)
Dapagliflozin0.35
Placebo0.99

Low Density Lipoproteins (c-LDL) at Week 12

The c-LDL levels are going to be measured at week 12 with standardized techniques. (NCT02113241)
Timeframe: Week 12

Interventionmmol/L (Mean)
Dapagliflozin3.1
Placebo2.8

Matsuda Index (Total Insulin Sensitivity) at Week 12.

Matsuda Index value is used to indicate insulin resistance on diabetes. Insulin sensitivity was calculated with Matsuda index [10,000 / √glucose 0' x insulin 0') (mean glucose oral glucose tolerance test (OGTT) x mean insulin OGTT)]. The entered values reflect the insulin sensitivity at week 12. (NCT02113241)
Timeframe: Week 12

Interventionindex (Mean)
Dapagliflozin2.7
Placebo1.6

Stumvoll Index (First Phase of Insulin Secretion) at Week 12.

"Human studies support the critical physiologic role of the first-phase of insulin secretion in the maintenance of postmeal glucose homeostasis.~First phase of insulin secretion was estimated using the Stumvoll index (1283+ 1.829 x insulin 30' - 138.7 x glucose 30' + 3.772 x insulin 0'), the entered values reflect the frst phase of insulin secretion at week 12." (NCT02113241)
Timeframe: Week 12

Interventionindex (Mean)
Dapagliflozin1463
Placebo2198

Systolic Blood Pressure at Week 12.

The systolic blood pressure is going to be evaluated at week 12 with a digital sphygmomanometer. (NCT02113241)
Timeframe: Week 12

InterventionmmHg (Mean)
Dapagliflozin117
Placebo121

Total Cholesterol at Week 12

The total cholesterol will be estimated by standardized techniques at week 12. (NCT02113241)
Timeframe: Week 12

Interventionmmol/L (Mean)
Dapagliflozin5.2
Placebo4.9

Triglycerides Levels at Week 12.

The triglycerides levels are going to be evaluated at week 12 with enzymatic-colorimetric techniques. (NCT02113241)
Timeframe: Week 12

Interventionmmol/L (Mean)
Dapagliflozin1.7
Placebo1.7

Uric Acid at Week 12.

The uric acid levels are going to be measured at week 12 with standardized techniques. (NCT02113241)
Timeframe: Week 12.

Interventionumol/L (Mean)
Dapagliflozin243.9
Placebo339.0

Waist Circumference at Week 12.

The waist circumference is going to be evaluated at week 12 with a flexible tape with standardized techniques. (NCT02113241)
Timeframe: Week 12

Interventioncentimeters (Mean)
Dapagliflozin97.6
Placebo97.2

Change in BMI

Change in BMI (body mass index) from study start to 16 weeks (NCT02613897)
Timeframe: Change from baseline to 16 weeks

InterventionKg/m^2 (Mean)
DAPA/SAXA (Dapagliflozin Plus Saxagliptin)-0.8
DAPA (Dapagliflozin Plus Placebo)-0.66
PCB (Placebo Plus Placebo)0.16

Change in Body Weight

Change in body weight from baseline to 16 weeks (NCT02613897)
Timeframe: Baseline to 16 weeks

InterventionKg (Mean)
DAPA/SAXA (Dapagliflozin Plus Saxagliptin)-2.28
DAPA (Dapagliflozin Plus Placebo)-1.76
PCB (Placebo Plus Placebo)0.26

Change in Fasting Plasma Glucagon (FPG)

A measure of the change in fasting plasma glucagon from study start to 16 weeks (NCT02613897)
Timeframe: Change from baseline to 16 weeks

Interventionmg/dl (Mean)
DAPA/SAXA (Dapagliflozin Plus Saxagliptin)-28.52
DAPA (Dapagliflozin Plus Placebo)26.89
PCB (Placebo Plus Placebo)6.88

Change in Free Fatty Acids (FFA)

Measure of change in Free Fatty Acids from study start to 16 weeks (NCT02613897)
Timeframe: Change from baseline to 16 weeks

InterventionmEq/L (Mean)
DAPA/SAXA (Dapagliflozin Plus Saxagliptin)-0.06
DAPA (Dapagliflozin Plus Placebo)-0.01
PCB (Placebo Plus Placebo)0.00

Change in Glucose Oxidation

Change in percentage of glucose oxidation from study start to 16 weeks (NCT02613897)
Timeframe: Change from baseline to 16 weeks

Interventionpercentage of oxidation (Mean)
DAPA/SAXA (Dapagliflozin Plus Saxagliptin)-22.07
DAPA (Dapagliflozin Plus Placebo)-46.54
PCB (Placebo Plus Placebo)4.65

Change in Lipid Oxidation

Change in lipid oxidation percentage from baseline to 16 weeks (NCT02613897)
Timeframe: Change from baseline to 16 weeks

Interventionpercentage of oxidation (Mean)
DAPA/SAXA (Dapagliflozin Plus Saxagliptin)-11.87
DAPA (Dapagliflozin Plus Placebo)22.02
PCB (Placebo Plus Placebo)-6.69

HBA1c

Change in blood glucose level measured over a 3 month period from study start to 16 weeks (NCT02613897)
Timeframe: Change from baseline to 16 weeks

Interventionpercentage change in blood glucose level (Mean)
DAPA/SAXA (Dapagliflozin Plus Saxagliptin)-1.67
DAPA (Dapagliflozin Plus Placebo)-1.46
PCB (Placebo Plus Placebo)0.44

Mean Oral Glucose Tolerance Test (OGTT)

Measure of change in OGTT from study start to 16 weeks (NCT02613897)
Timeframe: Change from baseline to 16 weeks

Interventionmg/dl (Mean)
DAPA/SAXA (Dapagliflozin Plus Saxagliptin)-49.62
DAPA (Dapagliflozin Plus Placebo)-44.24
PCB (Placebo Plus Placebo)20.26

Change in Endogenous Glucose Production (EGP)

All subjects received a Double-Tracer Oral Glucose Tolerance Test (OGTT) with 75g of glucose containing 14C-glucose together with intravenous primed-continuous infusion of 3(3H)-glucose for 240 minutes, at baseline (prior to) and after 16 weeks of therapy. Blood and urine samples were obtained during the OGTT to determine EGP. (NCT02613897)
Timeframe: Baseline and 16 weeks

,,
Interventionmg/kg*min (Mean)
Baseline Measurement16 weeks
DAPA (Dapagliflozin Plus Placebo)2.562.8
DAPA/SAXA (Dapagliflozin Plus Saxagliptin)2.452.4
PCB (Placebo Plus Placebo)1.952.15

Change From Baseline to 26-week Endpoint in Glycosylated Hemoglobin (HbA1c)

Least Squares (LS) means were calculated using analysis of covariance (ANCOVA) with country, treatment, and prior medication group (previous oral antihyperglycemic medication [OAM] versus no previous OAM) as fixed effects and baseline HbA1c as a covariate. (NCT01126580)
Timeframe: Baseline, 26 weeks

Interventionpercentage of glycosylated hemoglobin (Least Squares Mean)
1.5 mg LY2189265-0.78
0.75 mg LY2189265-0.71
Metformin-0.56

Change From Baseline to 52-week Endpoint in Glycosylated Hemoglobin (HbA1c)

Least Squares (LS) means were calculated using analysis of covariance (ANCOVA) with country, treatment, and prior medication group (previous oral antihyperglycemic medication [OAM] versus no previous OAM) as fixed effects and baseline HbA1c as a covariate. (NCT01126580)
Timeframe: Baseline, 52 weeks

Interventionpercentage of glycosylated hemoglobin (Least Squares Mean)
1.5 mg LY2189265-0.70
0.75 mg LY2189265-0.55
Metformin-0.51

Diabetes Treatment Satisfaction Questionnaire (DTSQ) Score, Change Version

The Diabetes Treatment Satisfaction Questionnaire change (DTSQc) score is used to assess relative change in participant satisfaction from baseline. The questionnaire consists of 8 items, 6 of which (1 and 4 through 8) assess treatment satisfaction. Each item is rated on a 7-point Likert scale. The scores from the 6 treatment satisfaction items are summed to a Total Treatment Satisfaction Score, which ranges from -18 (much less satisfied) to +18 (much more satisfied). Least Squares (LS) means of change from baseline were calculated using analysis of covariance (ANCOVA) adjusted by treatment, country, prior medication group, gender, and baseline score. (NCT01126580)
Timeframe: 52 weeks

Interventionunits on a scale (Least Squares Mean)
1.5 mg LY218926512.92
0.75 mg LY218926512.73
Metformin12.58

Measurement of LY2189265 Drug Concentration for Pharmacokinetics: Area Under the Concentration Curve (AUC)

Evaluable pharmacokinetic concentrations from the 4-week, 13-week, 26-week, and 52-week timepoints were combined and utilized in a population approach to determine the population mean estimate and standard deviation at steady-state. (NCT01126580)
Timeframe: 4 weeks, 13 weeks, 26 weeks, and 52 weeks

Interventionnanogram hours per milliliter (ng*hr/mL) (Mean)
1.5 mg LY218926512036
0.75 mg LY21892655919

Number of Participants With Adjudicated Pancreatitis at 52 Weeks Plus 30-day Follow up

The number of participants with pancreatitis confirmed by adjudication is summarized cumulatively at 52 weeks plus 30-day follow up. A summary of serious and other non-serious adverse events regardless of causality is located in the Reported Adverse Events module. (NCT01126580)
Timeframe: Baseline through 52 weeks plus 30-day follow up

Interventionparticipants (Number)
1.5 mg LY21892650
0.75 mg LY21892650
Metformin0

Number of Participants With Treatment Emergent Anti-LY2189265 Antibodies

A participant was considered to have treatment emergent LY2189265 anti-drug antibodies (ADA) if the participant had at least one titer that was treatment-emergent relative to baseline, defined as a 4-fold or greater increase in titer from baseline measurement. The total number of treatment emergent ADA was not analyzed at 26 weeks. (NCT01126580)
Timeframe: Baseline through 52 weeks

Interventionparticipants (Number)
1.5 mg or 0.75 mg LY218926510

Change From Baseline to 26 and 52 Weeks in Blood Pressure

Sitting systolic blood pressure (SBP) and sitting diastolic blood pressure (DBP) were measured. Least Squares (LS) means of change from baseline were calculated using a mixed-effects model for repeated measures (MMRM) with treatment, country, prior medication group, visit, and treatment-by-visit interaction as fixed effects, baseline interval as a covariate, and participant as a random effect. (NCT01126580)
Timeframe: Baseline, 26 weeks, and 52 weeks

,,
Interventionmilliliters of mercury (mmHg) (Least Squares Mean)
SBP, 26 weeks (n=244, 251, 239)SBP, 52 weeks (n=221, 219, 215)DBP, 26 weeks (n=244, 251, 239)DBP, 52 weeks (n=221, 219, 215)
0.75 mg LY2189265-2.61-2.74-1.02-1.37
1.5 mg LY2189265-1.89-0.110.050.31
Metformin-0.91-0.98-0.64-0.38

Change From Baseline to 26 and 52 Weeks in Body Mass Index (BMI)

Body mass index is an estimate of body fat based on body weight divided by height squared. Least Squares (LS) means were calculated using analysis of covariance (ANCOVA) with country, treatment, and prior medication group as fixed effects and baseline BMI as a covariate. (NCT01126580)
Timeframe: Baseline, 26 weeks, and 52 weeks

,,
Interventionkilograms per meter squared (kg/m^2) (Least Squares Mean)
26 weeks52 weeks
0.75 mg LY2189265-0.51-0.42
1.5 mg LY2189265-0.86-0.73
Metformin-0.82-0.83

Change From Baseline to 26 and 52 Weeks in Body Weight

Least Squares (LS) means were calculated using analysis of covariance (ANCOVA) with country, treatment, and prior medication group as fixed effects and baseline body weight as a covariate. (NCT01126580)
Timeframe: Baseline, 26 weeks, and 52 weeks

,,
Interventionkilograms (kg) (Least Squares Mean)
26 weeks (n=267, 269, 267)52 weeks (n=267, 269, 267)
0.75 mg LY2189265-1.36-1.09
1.5 mg LY2189265-2.29-1.93
Metformin-2.22-2.20

Change From Baseline to 26 and 52 Weeks in Daily Mean Blood Glucose Values From the 8-point Self-monitored Blood Glucose (SMBG) Profiles

The SMBG data were collected at the following 8 time points: pre-morning meal; 2 hours post-morning meal; pre-midday meal; 2 hours post-midday meal; pre-evening; 2 hours post-evening meal; bedtime; and 3AM or 5 hours after bedtime. Least Squares (LS) means of the mean of the 8 time points (daily mean) were calculated using analysis of covariance (ANCOVA) with country, treatment, and prior medication group as fixed effects and baseline daily mean as a covariate. (NCT01126580)
Timeframe: Baseline, 26 weeks, and 52 weeks

,,
Interventionmillimoles per liter (mmol/L) (Least Squares Mean)
26 weeks (n=195, 200, 211)52 weeks (n=197, 200, 212)
0.75 mg LY2189265-1.75-1.71
1.5 mg LY2189265-1.98-1.99
Metformin-1.68-1.58

Change From Baseline to 26 and 52 Weeks in Electrocardiogram Parameters, Fridericia Corrected QT (QTcF) Interval and PR Interval

The QT interval is a measure of the time between the start of the Q wave and the end of the T wave and was calculated from electrocardiogram (ECG) data using Fridericia's formula: QTc = QT/RR^0.33. Corrected QT (QTc) is the QT interval corrected for heart rate and RR, which is the interval between two R waves. PR is the interval between the P wave and the QRS complex. Least Squares (LS) means of change from baseline were calculated using a mixed-effects model for repeated measures (MMRM) with treatment, country, prior medication group, visit, and treatment-by-visit interaction as fixed effects, baseline interval as a covariate, and participant as a random effect. (NCT01126580)
Timeframe: Baseline, 26 weeks, and 52 weeks

,,
Interventionmilliseconds (msec) (Least Squares Mean)
QTcF interval, 26 weeks (n=230, 237, 221)QTcF interval, 52 weeks (n=212, 212, 205)PR interval, 26 weeks (n=226, 235, 218)PR interval, 52 weeks (n=209, 210, 201)
0.75 mg LY21892651.380.73-0.011.53
1.5 mg LY21892652.603.76-0.041.15
Metformin-0.91-0.53-2.04-2.88

Change From Baseline to 26 and 52 Weeks in Electrocardiogram Parameters, Heart Rate

Electrocardiogram (ECG) heart rate was measured. Least Squares (LS) means of change from baseline were calculated using a mixed-effects model for repeated measures (MMRM) with treatment, country, prior medication group, visit, and treatment-by-visit interaction as fixed effects and baseline interval as a covariate. (NCT01126580)
Timeframe: Baseline, 26 weeks, and 52 weeks

,,
Interventionbeats per minute (bpm) (Least Squares Mean)
26 weeks (n=230, 237, 221)52 weeks (n=212, 212, 205)
0.75 mg LY21892652.572.36
1.5 mg LY21892651.602.02
Metformin0.821.27

Change From Baseline to 26 and 52 Weeks in Fasting Blood Glucose

Least Squares (LS) means of change from baseline were calculated using a mixed-effects model for repeated measures (MMRM) with treatment, country, prior medication group, visit, and treatment-by-visit interaction as fixed effects, baseline fasting blood glucose as a covariate, and participant as a random effect. (NCT01126580)
Timeframe: Baseline, 26 weeks, and 52 weeks

,,
Interventionmillimoles per liter (mmol/L) (Least Squares Mean)
26 weeks (n=244, 247, 245)52 weeks (n=207, 210, 194)
0.75 mg LY2189265-1.46-1.00
1.5 mg LY2189265-1.61-1.56
Metformin-1.34-1.15

Change From Baseline to 26 and 52 Weeks in Homeostasis Model Assessment of Beta-cell Function

The homeostatic model assessment (HOMA) quantifies insulin resistance and beta-cell function. HOMA2-B is a computer model that uses fasting plasma insulin and glucose concentrations to estimate steady-state beta cell function (%B) as a percentage of a normal reference population (normal young adults). HOMA2-S is a computer model that uses fasting plasma insulin and glucose concentrations to estimate insulin sensitivity (%S) as percentages of a normal reference population (normal young adults). The normal reference populations were set at 100%. Least Squares (LS) means of change from baseline were calculated using a mixed-effects model for repeated measures (MMRM) with treatment, country, prior medication group, visit, and treatment-by-visit interaction as fixed effects, baseline HOMA2 as a covariate, and participant as a random effect. (NCT01126580)
Timeframe: Baseline, 26 weeks, and 52 weeks

,,
Interventionpercentage of HOMA2 (Least Squares Mean)
HOMA2-%B, 26 weeks (n=207, 207, 215)HOMA2-%B, 52 weeks (n=179, 185, 170)HOMA2-%S, 26 weeks (n=207, 207, 215)HOMA2-%S, 52 weeks (n=179, 185, 170)
0.75 mg LY218926528.9622.52.711.84
1.5 mg LY218926536.5529.970.955.29
Metformin14.119.779.9910.83

Change From Baseline to 26 and 52 Weeks in Pancreatic Enzymes

Amylase (total and pancreas-derived [PD]) and lipase concentrations were measured. (NCT01126580)
Timeframe: Baseline, 26 weeks, and 52 weeks

,,
Interventionunits per liter (U/L) (Median)
Amylase (total), 26 weeksAmylase (total), 52 weeksAmylase (PD), 26 weeksAmylase (PD), 52 weeksLipase, 26 weeksLipase, 52 weeks
0.75 mg LY21892656.005.004.003.005.005.00
1.5 mg LY21892657.005.505.004.007.005.00
Metformin4.004.001.002.001.001.00

Change From Baseline to 26 and 52 Weeks in Pulse Rate

Sitting pulse rate was measured. Least Squares (LS) means of change from baseline were calculated using a mixed-effects model for repeated measures (MMRM) with treatment, country, prior medication group, visit, and treatment-by-visit interaction as fixed effects, baseline interval as a covariate, and participant as a random effect. (NCT01126580)
Timeframe: Baseline, 26 weeks, and 52 weeks

,,
Interventionbeats per minute (bpm) (Least Squares Mean)
26 weeks (n=244, 251, 239)52 weeks (n=221, 219, 215)
0.75 mg LY21892652.141.63
1.5 mg LY21892652.391.84
Metformin1.591.12

Change From Baseline to 26 and 52 Weeks in Serum Calcitonin

(NCT01126580)
Timeframe: Baseline, 26 weeks, and 52 weeks

,,
Interventionpicograms per milliliter (pcg/mL) (Median)
26 weeks52 weeks
0.75 mg LY21892650.000.00
1.5 mg LY21892650.000.00
Metformin0.000.00

Change From Baseline to 26 and 52 Weeks in the Diabetes Symptoms Checklist Participant-reported Outcome (DSC-r) Score

"The Diabetes Symptoms Checklist-revised (DSC-r) was designed to assess the presence and perceived burden of diabetes-related symptoms. Respondents were to consider troublesomeness of 34 symptoms on a 5-point scale ranging from 5=extremely to 1=not at all. For symptoms/side-effects not experienced, the item was scored as 0. Symptoms were grouped into the following subscales: psychology-fatigue, psychology-cognitive, neurology-pain, neurology-sensory, cardiology, ophthalmology, hypoglycemia, and hyperglycemia. Subscale scores were calculated as the sum of the given subscale divided by the total number of items in the scale. Total score was computed from the sum of the 8 subscales and ranged from 0 to 40. Higher scores indicate greater symptom burden. Least Squares (LS) means of change from baseline were calculated using analysis of covariance (ANCOVA) adjusted by treatment, country, prior medication group, gender, and baseline score." (NCT01126580)
Timeframe: Baseline, 26 weeks, and 52 weeks

,,
Interventionunits on a scale (Least Squares Mean)
26 weeks (n=245, 253, 248)52 weeks (n=247, 255, 249)
0.75 mg LY2189265-0.160.42
1.5 mg LY21892650.240.49
Metformin0.410.59

Change From Baseline to 26 and 52 Weeks in the Diabetes Treatment Satisfaction Questionnaire (DTSQ) Score, Status Version

The Diabetes Treatment Satisfaction Questionnaire status version (DTSQs) is used to assess participant treatment satisfaction at each study visit. The questionnaire consists of 8 items, 6 of which (1 and 4 through 8) assess treatment satisfaction. Each item is rated on a 7-point Likert scale. Scores from the 6 treatment satisfaction items are summed to a Total Treatment Satisfaction Score, which ranges from 0 (very dissatisfied) to 36 (very satisfied). Least Squares (LS) means of change from baseline were calculated using analysis of covariance (ANCOVA) adjusted by treatment, country, prior medication group, gender, and baseline score. (NCT01126580)
Timeframe: Baseline, 26 weeks, and 52 weeks

,,
Interventionunits on a scale (Least Squares Mean)
26 weeks (n=244, 249, 241)52 weeks (n=245, 251, 244)
0.75 mg LY21892651.811.29
1.5 mg LY21892651.931.82
Metformin2.041.94

Change From Baseline to 26 and 52 Weeks in the Impact of Weight on Activities of Daily Living (IW-ADL) Score

"The Impact of Weight on Activities of Daily Living (renamed the Ability to Perform Physical Activities of Daily Living [APPADL]) questionnaire contains 7 items that assess how difficult it is for participants to engage in certain activities considered to be integral to normal daily life, such as walking, standing and climbing stairs. Items are scored on a 5-point numeric rating scale where 5 = not at all difficult and 1 = unable to do. The individual scores from all 7 items are summed and a single total score is calculated and may range between 7 and 35. A higher score indicates better ability to perform activities of daily living. Least Squares (LS) means of change from baseline were calculated using analysis of covariance (ANCOVA) adjusted by treatment, country, prior medication group, gender, and baseline score." (NCT01126580)
Timeframe: Baseline, 26 weeks, and 52 weeks

,,
Interventionunits on a scale (Least Squares Mean)
26 weeks (n=247, 251, 247)52 weeks (n=247, 252, 248)
0.75 mg LY21892650.19-0.05
1.5 mg LY21892650.090.39
Metformin0.020.28

Change From Baseline to 26 and 52 Weeks in the Impact of Weight on Self-Perception (IW-SP) Score

The Impact of Weight on Self-Perception (IW-SP) questionnaire contains 3 items that assess how often the participants' body weight affects how happy they are with their appearance and how often they feel self-conscious when out in public. Items are scored on a 5-point numeric rating scale where 5 = never and 1 = always. A single total score is calculated by summing the scores for all 3 items. Total score ranges between 3 and 15, where a higher score is indicative of better self-perception. Least Squares (LS) means of change from baseline were calculated using analysis of covariance (ANCOVA) adjusted by treatment, country, prior medication group, gender, and baseline score. (NCT01126580)
Timeframe: Baseline, 26 weeks, and 52 weeks

,,
Interventionunits on a scale (Least Squares Mean)
26 weeks (n=248, 254, 249)52 weeks (n=249, 255, 250)
0.75 mg LY21892650.630.61
1.5 mg LY21892650.720.45
Metformin0.790.75

Number of Participants With Adjudicated Cardiovascular Events at 52 Weeks Plus 30-day Follow up

Information on cardiovascular (CV) risk factors was collected at baseline. Data on any new CV event was prospectively collected using a CV event electronic case report form. Deaths and nonfatal cardiovascular adverse events (AEs) were adjudicated by an external committee of physicians with cardiology expertise. Nonfatal cardiovascular AEs to be adjudicated included myocardial infarction, hospitalization for unstable angina, hospitalization for heart failure, coronary interventions, and cerebrovascular events, including cerebrovascular accident (stroke) and transient ischemic attack. The number of participants with CV events confirmed by adjudication is summarized cumulatively at 52 weeks plus 30-day follow up. Serious and all other non-serious adverse events regardless of causality are summarized in the Reported Adverse Events module. (NCT01126580)
Timeframe: Baseline through 52 weeks plus 30-day follow up

,,
Interventionparticipants (Number)
Any CV EventAny Fatal CV EventAny Nonfatal CV Event
0.75 mg LY2189265202
1.5 mg LY2189265101
Metformin101

Number of Participants With Treatment Emergent Adverse Events at 26 and 52 Weeks

A treatment-emergent adverse event (TEAE) was defined as an event that first occurs or worsens (increases in severity) after baseline regardless of causality or severity. The number of participants with one or more TEAE is summarized cumulatively at 26 and 52 weeks. A summary of serious and other non-serious adverse events regardless of causality is located in the Reported Adverse Events module. (NCT01126580)
Timeframe: 26 weeks and 52 weeks

,,
Interventionparticipants (Number)
26 weeks52 weeks
0.75 mg LY2189265150177
1.5 mg LY2189265163179
Metformin151170

Number of Self-reported Hypoglycemic Events at 26 and 52 Weeks

Hypoglycemic events were classified as severe (defined as episodes requiring the assistance of another person to actively administer resuscitative actions), documented symptomatic (defined as any time a participant feels that he/she is experiencing symptoms and/or signs associated with hypoglycemia, and has a plasma glucose level of less than or equal to 70 milligrams per deciliter [mg/dL]), or asymptomatic (defined as events not accompanied by typical symptoms of hypoglycemia but with a measured plasma glucose of less than or equal to 70 mg/dL). A summary of serious and other non-serious adverse events regardless of causality is located in the Reported Adverse Events module. (NCT01126580)
Timeframe: Baseline through 26 weeks and 52 weeks

,,
Interventionevents (Number)
Severe, 26 weeks (n=241, 248, 236)Severe, 52 weeks (n=214, 217, 199)Documented Symptomatic, 26 weeks (n=241, 248, 236)Documented Symptomatic, 52 weeks (n=214, 217, 199)Asymptomatic, 26 weeks (n=241, 248, 236)Asymptomatic, 52 weeks (n=214, 217, 199)
0.75 mg LY2189265006899
1.5 mg LY21892650027195
Metformin0022139

Percent Change From Baseline to 26 and 52 Weeks in Total Cholesterol

Percent changes in total cholesterol were assessed using analysis of variance (ANOVA) on the rank-transformed data with only treatment included in the model. (NCT01126580)
Timeframe: Baseline, 26 weeks, and 52 weeks

,,
Interventionpercentage change in total cholesterol (Median)
26 weeks (n=244, 244, 243)52 weeks (n=247, 248, 245)
0.75 mg LY2189265-1.77-0.78
1.5 mg LY2189265-3.86-1.69
Metformin-3.51-3.88

Percentage Change From Baseline to 26 and 52 Weeks in High Density Lipoprotein Cholesterol (HDL-C)

Percentage changes in HDL-C were assessed using analysis of variance (ANOVA) on the rank-transformed data with only treatment included in the model. (NCT01126580)
Timeframe: Baseline, 26 weeks, and 52 weeks

,,
Interventionpercentage change in HDL-C (Median)
26 weeks (n=246, 244, 244)52 weeks (n=248, 248, 246)
0.75 mg LY21892654.202.31
1.5 mg LY21892652.394.95
Metformin5.784.32

Percentage Change From Baseline to 26 and 52 Weeks in Low Density Lipoprotein Cholesterol (LDL-C)

Percentage changes in LDL-C were assessed using analysis of variance (ANOVA) on the rank-transformed data with only treatment included in the model. (NCT01126580)
Timeframe: Baseline, 26 weeks, and 52 weeks

,,
Interventionpercentage change in LDL-C (Median)
26 weeks (n=233, 231, 221)52 weeks (n=236, 240, 231)
0.75 mg LY2189265-2.70-2.34
1.5 mg LY2189265-6.86-2.06
Metformin-8.97-7.23

Percentage Change From Baseline to 26 and 52 Weeks in Triglycerides

Percentage changes in triglycerides were assessed using analysis of variance (ANOVA) on the rank-transformed data with only treatment included in the model. (NCT01126580)
Timeframe: Baseline, 26 weeks, and 52 weeks

,,
Interventionpercentage change in triglycerides (Median)
26 weeks (n=252, 252, 253)52 weeks (n=255, 256, 254)
0.75 mg LY2189265-1.96-0.86
1.5 mg LY2189265-2.35-4.27
Metformin2.561.91

Percentage of Participants Achieving a Glycosylated Hemoglobin (HbA1c) of Less Than 7% and Less Than or Equal to 6.5% at 26 and 52 Weeks

The percentage of participants achieving HbA1c level less than 7.0% and less than or equal to 6.5% was analyzed with a logistic regression model with baseline, prior medication group, and treatment as factors included in the model. (NCT01126580)
Timeframe: 26 weeks and 52 weeks

,,
Interventionpercentage of participants (Number)
HbA1c less than 7%, 26 weeksHbA1c less than or equal to 6.5%, 26 weeksHbA1c less than 7%, 52 weeksHbA1c less than or equal to 6.5%, 52 weeks
0.75 mg LY218926562.640.053.234.7
1.5 mg LY218926561.546.060.042.3
Metformin53.629.848.328.3

Rate of Self-reported Hypoglycemic Events at 52 Weeks

Hypoglycemic events were classified as severe (defined as episodes requiring the assistance of another person to actively administer resuscitative actions), documented symptomatic (defined as any time a participant feels that he/she is experiencing symptoms and/or signs associated with hypoglycemia, and has a plasma glucose level of less than or equal to 70 milligrams per deciliter [mg/dL]), or asymptomatic (defined as events not accompanied by typical symptoms of hypoglycemia but with a measured plasma glucose of less than or equal to 70 mg/dL). The 1-year adjusted rate of hypoglycemic events is summarized cumulatively at 52 weeks. A summary of serious and other non-serious adverse events regardless of causality is located in the Reported Adverse Events module. (NCT01126580)
Timeframe: Baseline through 52 weeks

,,
Interventionevents per participant per year (Mean)
SevereDocumented SymptomaticAsymptomatic
0.75 mg LY21892650.000.150.30
1.5 mg LY21892650.000.620.24
Metformin0.000.090.18

Change in Percent of Blood Glucose (BG) Within Target

Percent of BG between 70 and 180 mg/dL, as measured using Continuous Glucose Monitor (CGM) (NCT03199638)
Timeframe: baseline vs. at 3 months

,
InterventionPercentage of Blood Glucose (Mean)
baselineat 3 months
an Exercise + Glutamine Group57.669.2
an Exercise Group63.746.4

Change in the Mean Amplitude of Glycemic Excursions (MAGE)

MAGE describes the average amplitude of glycemic variations measured using continuous glucose monitoring (CGM) (NCT03199638)
Timeframe: before vs. at 3 months

,
Interventionmg/dL (Mean)
baselineat 3 months
an Exercise + Glutamine Group108123
an Exercise Group129139

HbA1c, Glycated Hemoglobin

change in glycated hemoglobin (NCT03199638)
Timeframe: baseline vs. at 3 months

,
Interventionpercentage of total hemoglobin (Mean)
baselineat 3 months
an Exercise + Glutamine Group8.38.4
an Exercise Group7.98.0

Insulin Dose

Change in insulin dose (Units/kg/day) used at home (NCT03199638)
Timeframe: baseline vs. at 3 months

,
InterventionUnits/kg/day (Mean)
baselineat 3 months
an Exercise + Glutamine Group0.981.0
an Exercise Group1.00.8

Insulin Sensitivity Score (ISS)

Change in insulin sensitivity score, determined using SEARCH ISS model published equation: logeIS = 4.64725 - 0.02032 × (waist, cm) - 0.09779 × (HbA1c, %) - 0.00235 × (Triglycerides, mg/dL). The range of ISS scores is between 1-15. Higher scores imply a better insulin sensistivity. (NCT03199638)
Timeframe: baseline vs. at 3 months

,
Interventionscore on a scale (Mean)
baselineat 3 months
an Exercise + Glutamine Group2.102.16
an Exercise Group2.172.20

Percent Blood Glucose (BG) >180

Change in Percent of BG above 180 mg, as determined using Continuous Glucose Monitor (CGM) (NCT03199638)
Timeframe: baseline vs. at 3 months

,
InterventionPercentage of Blood Glucose (Mean)
baslineat 3 months
an Exercise + Glutamine Group39.426.6
an Exercise Group29.146.4

Percent of BG <70 mg/dL

Change in Percent of BG below 70 mg/dL, as determined by Continuous Glucose Monitor (CGM) (NCT03199638)
Timeframe: baseline vs. at 3 months

,
InterventionPercentage of Blood Glucose (Mean)
baselineat 3 months
an Exercise + Glutamine Group3.14.4
an Exercise Group7.27.2

Change in Body Weight From Baseline to Week 30.

Change in body weight from baseline to Week 30 using MMRM model.The model included the respective baseline outcome as covariate, treatment, country, prior use of SUs, week of visit, and treatment-by-week interaction as fixed effects and patient and error as random effects. (NCT00960661)
Timeframe: baseline, week 30

Interventionkg (Least Squares Mean)
Exenatide (BET)-2.45
Insulin Lispro (BBT)2.11

Change in Diastolic Blood Pressure (DBP) From Baseline to Week 30

Change in Diastolic Blood Pressure (DBP) from baseline to Week 30 using MMRM model.The model included the respective baseline outcome as covariate, treatment, country, prior use of SUs, week of visit, and treatment-by-week interaction as fixed effects and patient and error as random effects. (NCT00960661)
Timeframe: baseline, Week 30

InterventionmmHg (Least Squares Mean)
Exenatide (BET)-0.64
Insulin Lispro (BBT)-0.14

Change in Fasting Blood Glucose (FBG) From Baseline to Week 30.

Change in fasting blood glucose (FBG) from Baseline to Week 30 using MMRM model. The model included the respective baseline outcome as covariate, treatment, country, prior use of SUs, week of visit, and treatment-by-week interaction as fixed effects and patient and error as random effects. (NCT00960661)
Timeframe: Baseline, Week 30

Interventionmmol/L (Least Squares Mean)
Exenatide (BET)-0.46
Insulin Lispro (BBT)0.18

Change in Glycosylated Hemoglobin (HbA1c) From Baseline to Week 30

Change in HbA1c from baseline following 30 weeks of therapy (i.e. HbA1c at week 30 minus HbA1c at baseline). (NCT00960661)
Timeframe: Baseline, 30 weeks

Interventionpercent of hemoglobin (Least Squares Mean)
Exenatide (BET)-1.13
Insulin Lispro (BBT)-1.10

Change in High Density Lipoprotein (HDL) From Baseline to Week 30

Change in High Density Lipoprotein (HDL) from baseline to Week 30 using ANCOVA model.The model included the respective secondary outcome as dependent variable, country, prior use of SU's and treatment groups as factors, and the respective outcomes baseline value as a covariate. (NCT00960661)
Timeframe: Baseline, week 30

Interventionmmol/L (Least Squares Mean)
Exenatide (BET)-0.04
Insulin Lispro (BBT)0.03

Change in Low Density Lipoprotein (LDL) From Baseline to Week 30

Change in Low Density Lipoprotein (LDL) from baseline to week 30 using ANCOVA model.The model included the respective secondary outcome as dependent variable, country, prior use of SU's and treatment groups as factors, and the respective outcomes baseline value as a covariate. (NCT00960661)
Timeframe: Baseline, Week 30

Interventionmmol/L (Least Squares Mean)
Exenatide (BET)-0.12
Insulin Lispro (BBT)-0.03

Change in Systolic Blood Pressure (SBP) From Baseline to Week 30

Change in Systolic Blood Pressure (SBP) from baseline to Week 30 using MMRM model.The model included the respective baseline outcome as covariate, treatment, country, prior use of SUs, week of visit, and treatment-by-week interaction as fixed effects and patient and error as random effects. (NCT00960661)
Timeframe: Baseline, Week 30

InterventionmmHg (Least Squares Mean)
Exenatide (BET)-4.13
Insulin Lispro (BBT)0.37

Change in Total Cholesterol From Baseline to Week 30

Change in total cholesterol from baseline to Week 30 using ANCOVA model. The model included the respective secondary outcome as dependent variable, country, prior use of SU's and treatment groups as factors, and the respective outcomes baseline value as a covariate. (NCT00960661)
Timeframe: Baseline, week 30

Interventionmmol/L (Least Squares Mean)
Exenatide (BET)-0.14
Insulin Lispro (BBT)-0.03

Major Hypoglycemia Rate Per Year

Mean (standard deviation) of major hyperglycemia episodes experienced per year. Rates per year were calculated for each individual as the number of episodes divided by the total number of days in the study (from randomization to last visit date), then multiplied by 365.25. Major hypoglycemia was defined as any symptoms consistent with hypoglycemia resulting in loss of consciousness or seizure that shows prompt recovery in response to administration of glucagon or glucose OR documented hypoglycemia (blood glucose <3.0 mmol/L [54 mg/dL]) and requiring the assistance of another person because of severe impairment in consciousness or behavior. (NCT00960661)
Timeframe: 30 weeks

Interventionrate per year (Mean)
Exenatide (BET)0.0
Insulin Lispro (BBT)0.1

Minor Hypoglycemia Rate Per Year

Mean (standard deviation) of minor hyperglycemia episodes experienced per year. Rates per year were calculated for each individual as the number of episodes divided by the total number of days in the study (from randomization to last visit date), then multiplied by 365.25. Minor hypoglycemia was defined as any time a participant feels that he or she is experiencing a sign or symptom associated with hypoglycemia that is either self-treated by the participant or resolves on its own AND has a concurrent finger stick blood glucose <3.0 mmol/L (54 mg/dL) (NCT00960661)
Timeframe: 30 weeks

Interventionrate per year (Mean)
Exenatide (BET)2.1
Insulin Lispro (BBT)5.0

Percent of Participants Achieving HbA1c ≤ 6.5%.

Percent of participants achieving HbA1c ≤ 6.5%. (NCT00960661)
Timeframe: Week 30

Interventionpercentage of participants (Number)
Exenatide (BET)26.2
Insulin Lispro (BBT)25.5

Percentage of Participants Achieving HbA1C < 7.0%

Percentage of participants achieving HbA1C < 7.0% (NCT00960661)
Timeframe: Week 30

InterventionPercentage of participants (Number)
Exenatide (BET)46.7
Insulin Lispro (BBT)42.6

Daily Insulin Glargine Dose at Baseline and at Week 30

Daily Insulin Glargine Dose at baseline and at Week 30 (NCT00960661)
Timeframe: Baseline, week 30

,
InterventionIU/day (Mean)
BaselineWeek 30
Exenatide (BET)61.556.9
Insulin Lispro (BBT)61.151.5

Change in A1c at the End of Study Period

change in A1c (%) from baseline to end of study at 16 weeks (NCT02846233)
Timeframe: 16 weeks (from baseline to end of study at 16 weeks)

Intervention% change of A1c (Mean)
Treatment Group-2.38
Control Group-0.83

Changes in Blood Pressure

change (mmHg) of systolic BP from baseline to the end of study at 16 weeks (NCT02846233)
Timeframe: 16 weeks (from baseline to end of study at 16 weeks)

InterventionmmHg (Mean)
Treatment Group-16
Control Group15

Changes in Heart Rate

change (beats/min) from baseline to the end of study at 16 weeks (NCT02846233)
Timeframe: 16 weeks

Interventionbeats per min (Mean)
Treatment Group4.3
Control Group5.13

Changes in LDL

change (mg/dL) from baseline to the end of study at 16 weeks (NCT02846233)
Timeframe: 16 weeks (from baseline to end of study at 16 weeks)

Interventionmg/dL (Mean)
Treatment Group-15.7
Control Group21

Changes in Serum Creatinine

change (mg/dL) from baseline to the end of study at 16 weeks (NCT02846233)
Timeframe: 16 weeks (from baseline to end of study at 16 weeks)

Interventionmg/dL (Mean)
Treatment Group0.04
Control Group0.04

Changes in Total Cholesterol

change (mg/dL) from baseline to the end of study at 16 weeks (NCT02846233)
Timeframe: 16 weeks (from baseline to end of study at 16 weeks)

Interventionmg/dL (Mean)
Treatment Group-18.5
Control Group18.38

Changes in Treatment Satisfaction Scores (DM-SAT Total Score)

"Patient satisfaction with treatment in both groups will be measured by the validated the Diabetes Medications Satisfaction Tool (DM-SAT). Response options range from 0=not at all satisfied to 10=extremely satisfied and a total score is calculated ranging from 0 to 100, with higher scores indicating more diabetes medication satisfaction." (NCT02846233)
Timeframe: 16 weeks (from baseline to end of study at 16 weeks)

Interventionscore on a scale (Mean)
Treatment Group45.3
Control Group4.63

Changes in Weight

change (in pounds) from baseline to the end of study at 16 weeks (NCT02846233)
Timeframe: 16 weeks (from baseline to end of study at 16 weeks)

Interventionpounds (Mean)
Treatment Group-16.38
Control Group-0.1

Adjusted Mean Change in Fasting Plasma Glucose (FPG) From Baseline to Week 1

To compare the change from baseline in fasting plasma glucose (FPG) achieved with each of the 2 BID doses of dapagliflozin (2.5 mg BID and 5 mg BID) co-administered with metformin versus placebo co-administered with metformin after 1 week of double-blind treatment. (NCT01217892)
Timeframe: Baseline to Week 1

Interventionmg/dL (Least Squares Mean)
Dapagliflozin 2.5mg BID Plus Metformin-13.7
Dapagliflozin 5mg BID Plus Metformin-14.7
Dapagliflozin 10mg OD Plus Metformin-15.5
Placebo Plus Metformin2.0

Adjusted Mean Change in Fasting Plasma Glucose (FPG) From Baseline to Week 16

To compare the change from baseline in fasting plasma glucose (FPG) achieved with each of the 2 BID doses of dapagliflozin (2.5 mg BID and 5 mg BID) co-administered with metformin versus placebo co-administered with metformin after 16 weeks of double-blind treatment. (NCT01217892)
Timeframe: Baseline to Week 16

Interventionmg/dL (Least Squares Mean)
Dapagliflozin 2.5mg BID Plus Metformin-20.8
Dapagliflozin 5mg BID Plus Metformin-25.6
Dapagliflozin 10mg OD Plus Metformin-20.4
Placebo Plus Metformin-10.4

Adjusted Mean Change in HbA1c Levels

To compare the change from baseline in HbA1c achieved with each of the 2 BID doses of dapagliflozin (2.5 mg BID and 5 mg BID) co-administered with metformin versus placebo co-administered with metformin after 16 weeks of double-blind treatment. (NCT01217892)
Timeframe: Baseline to Week 16

InterventionPercent (Least Squares Mean)
Dapagliflozin 2.5mg BID Plus Metformin-0.52
Dapagliflozin 5mg BID Plus Metformin-0.65
Dapagliflozin 10mg OD Plus Metformin-0.59
Placebo Plus Metformin-0.30

Adjusted Percent Change in Body Weight

To compare the percent change from baseline in body weight achieved with each of the 2 BID doses of dapagliflozin (2.5 mg BID, and 5 mg BID) co-administered with metformin versus placebo co-administered with metformin after 16 weeks of double-blind treatment. (NCT01217892)
Timeframe: Baseline to Week 16

InterventionPercent (Least Squares Mean)
Dapagliflozin 2.5mg BID Plus Metformin-2.84
Dapagliflozin 5mg BID Plus Metformin-3.20
Dapagliflozin 10mg OD Plus Metformin-2.76
Placebo Plus Metformin-1.04

Proportion of Participants With HbA1c<7.0% at Week 16, in Participants Who Had HbA1c ≥7.0% at Baseline.

To compare the adjusted proportions controlling for baseline HbA1c [acc. to Zhang, Tsiatis & Davidian and Davidian, Tsiatis, Zhang & Lu] of participants with HbA1c <7.0% achieved with each of the 2 BID doses of dapagliflozin (2.5 mg BID and 5 mg BID) co-administered with metformin versus placebo co-administered with metformin after 16 weeks of double-blind treatment, in patients who had HbA1c ≥7.0% at baseline. (NCT01217892)
Timeframe: Baseline to Week 16

InterventionPercentage of participants (Least Squares Mean)
Dapagliflozin 2.5mg BID Plus Metformin33.6
Dapagliflozin 5mg BID Plus Metformin38.2
Dapagliflozin 10mg OD Plus Metformin28.1
Placebo Plus Metformin21.4

Change in HbA1c From Baseline to Week 104

The table below shows the least-squares (LS) mean change in HbA1c from Baseline to Week 104 for each treatment group. The statistical analyses show the treatment differences (ie, each canagliflozin group minus glimepiride) in the LS mean change. (NCT00968812)
Timeframe: Baseline, Week 104

InterventionPercent (Least Squares Mean)
Canagliflozin 100 mg-0.65
Canagliflozin 300 mg-0.74
Glimepiride-0.55

Change in HbA1c From Baseline to Week 52

The table below shows the least-squares (LS) mean change in HbA1c from Baseline to Week 52 for each treatment group. The statistical analyses show the treatment differences (ie, each canagliflozin group minus glimepiride) in the LS mean change. (NCT00968812)
Timeframe: Day 1 (Baseline) and Week 52

InterventionPercent (Least Squares Mean)
Canagliflozin 100 mg-0.82
Canagliflozin 300 mg-0.93
Glimepiride-0.81

Percent Change in Body Weight From Baseline to Week 52

The table below shows the least-squares (LS) mean percent change in body weight from Baseline to Week 52 for each treatment group. The statistical analyses show the treatment differences (ie, each canagliflozin group minus glimepiride) in the LS mean percent change. (NCT00968812)
Timeframe: Day 1 (Baseline) and Week 52

InterventionPercent change (Least Squares Mean)
Canagliflozin 100 mg-4.2
Canagliflozin 300 mg-4.7
Glimepiride1.0

Percentage of Patients Experiencing at Least 1 Hypoglycemic Event From Baseline to Week 52

The table below shows the percentage of patients who experienced at least 1 documented hypoglycemic event from Baseline to Week 52 for each treatment group. The statistical analyses show the treatment differences (ie, each canagliflozin group minus glimepiride) in percentages. (NCT00968812)
Timeframe: Day 1 (Baseline) and Week 52

InterventionPercentage of patients (Number)
Canagliflozin 100 mg5.6
Canagliflozin 300 mg4.9
Glimepiride34.2

Adjusted Mean Change From Baseline in Fasting Plasma Glucose Levels at Week 1 (Last Observation Carried Forward [LOCF]): Group 1

Secondary endpoints were tested using a sequential testing procedure and are presented in hierarchical order. Because the primary focus of the entire dapagliflozin program was on morning dosing in a population with HbA1c ≥7% and ≤10%, only data on AM dosing were summarized. Data after rescue medication was excluded from this analysis. Fasting plasma glucose was measured by a central laboratory. Baseline was defined as the last assessment prior to the start date and time of the first dose of the double-blind study medication. In cases where time of the first dose or time of the assessment was not available, baseline was defined as the last assessment on or prior to the date of the first dose of the double-blind study medication. (NCT00528372)
Timeframe: Baseline to Week 1 (end of Short-term Period)

Interventionmg/dL (Mean)
Group 1: Dapagliflozin Placebo AM & PM-2.4
Group 1: Dapagliflozin, 2.5 mg AM-2.9
Group 1: Dapagliflozin, 5 mg AM-16.4
Group 1: Dapagliflozin, 10 mg AM-16.1
Group 1: Dapagliflozin, 2.5 mg PM-14.4
Group 1: Dapagliflozin, 5 mg PM-18.6
Group 1: Dapagliflozin, 10 mg PM-20.3

Adjusted Mean Change From Baseline in Fasting Plasma Glucose Levels at Week 1 (Last Observation Carried Forward [LOCF]): Group 2

Secondary endpoints were tested using a sequential testing procedure and are presented in hierarchical order. Because the primary focus of the entire dapagliflozin program was on morning dosing in a population with HbA1c ≥7% and ≤10%, only data on AM dosing were summarized. Data after rescue medication was excluded from this analysis. Fasting plasma glucose was measured by a central laboratory. Baseline was defined as the last assessment prior to the start date and time of the first dose of the double-blind study medication. In cases where time of the first dose or time of the assessment was not available, baseline was defined as the last assessment on or prior to the date of the first dose of the double-blind study medication. (NCT00528372)
Timeframe: Baseline to Week 1

Interventionmg/dL (Mean)
Group 2: Dapagliflozin, 5 mg AM-54.3
Group 2: Dapagliflozin, 10 mg AM-74.3

Adjusted Mean Change From Baseline in Hemoglobin A1c (HbA1c) in Participants With Baseline Body Mass Index (BMI) ≥27 kg/m^2 (Last Observation Carried Forward [LOCF])

Secondary endpoints were tested using a sequential testing procedure and are presented in hierarchical order. If no Week 24 assessment was available, HbA1c was recorded from the last postbaseline measurement prior to Week 24. Data after rescue medication was excluded from this analysis. Baseline was defined as the last assessment prior to the start date and time of the first dose of the double-blind study medication. In cases where time of the first dose or time of the assessment was not available, baseline was defined as the last assessment on or prior to the date of the first dose of the double-blind study medication. Group 2 (patients with enrollment baseline HbA1c >10% and ≤2%) was considered an exploratory group, included to obtain initial efficacy and safety data for these patients. No comparator arm was included. Thus, only key safety and efficacy analyses were performed for Group 2. (NCT00528372)
Timeframe: Baseline to Week 24 (end of Short-term Period)

InterventionPercent (Mean)
Group 1: Dapagliflozin Placebo AM & PM-0.21
Group 1: Dapagliflozin, 2.5 mg AM-0.58
Group 1: Dapagliflozin, 5 mg AM-0.73
Group 1: Dapagliflozin, 10 mg AM-0.88
Group 1: Dapagliflozin, 2.5 mg PM-0.81
Group 1: Dapagliflozin, 5 mg PM-0.76
Group 1: Dapagliflozin, 10 mg PM-0.80

Adjusted Mean Change From Baseline to Week 24 in Fasting Plasma Glucose Levels (Last Observation Carried Forward [LOCF]): Group 1

Secondary endpoints were tested using a sequential testing procedure and are presented in hierarchical order. Because the primary focus of the entire dapagliflozin program was on morning dosing in a population with HbA1c ≥7% and ≤10%, only data on AM dosing were summarized in secondary efficacy analyses. Data after rescue medication were excluded from this analysis. Baseline was defined as the last assessment prior to the start date and time of the first dose of the double-blind study medication. In cases where time of the first dose or time of the assessment was not available, baseline was defined as the last assessment on or prior to the date of the first dose of the double-blind study medication. If no Week 24 assessment was available, glucose levels were recorded from the last postbaseline measurement prior to Week 24. For rescued participants, measurements obtained after initiation of rescue medication was not considered in calculating the endpoint. (NCT00528372)
Timeframe: Baseline to Week 24 (end of Short-term Period)

Interventionmg/dL (Mean)
Group 1: Dapagliflozin Placebo AM & PM-4.1
Group 1: Dapagliflozin, 2.5 mg AM-15.2
Group 1: Dapagliflozin, 5 mg AM-24.1
Group 1: Dapagliflozin, 10 mg AM-28.8
Group 1: Dapagliflozin, 2.5 mg PM-25.6
Group 1: Dapagliflozin, 5 mg PM-27.3
Group 1: Dapagliflozin, 10 mg PM-29.6

Adjusted Mean Change From Baseline to Week 24 in Fasting Plasma Glucose Levels (Last Observation Carried Forward [LOCF]): Group 2

Group 2 was an exploratory group, included to obtain initial efficacy and safety data. No comparator arm was included. Secondary endpoints were tested using a sequential testing procedure and are presented in hierarchical order. Data after rescue medication were excluded from this analysis. Baseline was defined as the last assessment prior to the start date and time of the first dose of the double-blind study medication. In cases where time of the first dose or time of the assessment was not available, baseline was defined as the last assessment on or prior to the date of the first dose of the double-blind study medication. If no Week 24 assessment was available, glucose levels were recorded from the last postbaseline measurement prior to Week 24. For rescued participants, measurements obtained after initiation of rescue medication was not considered in calculating the endpoint. (NCT00528372)
Timeframe: Baseline to Week 24 (end of Short-term Period)

Interventionmg/dL (Mean)
Group 2: Dapagliflozin, 5 mg AM-77.
Group 2: Dapagliflozin, 10 mg AM-84.3

Adjusted Mean Change From Baseline to Week 24 in Hemoglobin A1C (HbA1c) (Last Observation Carried Forward [LOCF]): Group 1

HbA1c was measured by a central laboratory. Data after rescue medication was excluded from this analysis. Baseline was defined as the last assessment prior to the start date and time of the first dose of the double-blind study medication. In cases where time of the first dose or time of the assessment was not available, baseline was defined as the last assessment on or prior to the date of the first dose of the double-blind study medication. If no Week 24 assessment was available, the last postbaseline measurement prior to Week 24 was used. For rescued participants, measurements obtained after initiation of rescue medication were not considered in calculating the primary endpoint. Evening dosing groups were summarized as exploratory endpoints. (NCT00528372)
Timeframe: Baseline to Week 24 (end of Short-term Period)

InterventionPercent (Mean)
Group 1: Dapagliflozin Placebo AM & PM-0.23
Group 1: Dapagliflozin, 2.5 mg AM-0.58
Group 1: Dapagliflozin, 5 mg AM-0.77
Group 1: Dapagliflozin, 10 mg AM-0.89
Group 1: Dapagliflozin, 2.5 mg PM-0.83
Group 1: Dapagliflozin, 5 mg PM-0.79
Group 1: Dapagliflozin, 10 mg PM-0.79

Adjusted Mean Change From Baseline to Week 24 in Hemoglobin A1c (HbA1c) (Last Observation Carried Forward [LOCF]): Group 2

HbA1c was measured by a central laboratory. Data after rescue medication was excluded from this analysis. Baseline was defined as the last assessment prior to the start date and time of the first dose of the double-blind study medication. In cases where time of the first dose or time of the assessment was not available, baseline was defined as the last assessment on or prior to the date of the first dose of the double-blind study medication. If no Week 24 assessment was available, the last postbaseline measurement prior to Week 24 was used. For rescued participants, measurements obtained after initiation of rescue medication were not considered in calculating the primary endpoint. Group 2 (patients with enrollment baseline HbA1c >10% and ≤2%) was considered an exploratory group, included to obtain initial efficacy and safety data for these patients. No comparator arm was included. (NCT00528372)
Timeframe: Baseline to Week 24 (end of Short-term Period)

InterventionPercent (Mean)
Group 2: Dapagliflozin, 5 mg AM-2.88
Group 2: Dapagliflozin, 10 mg AM-2.66

Adjusted Mean Change From Baseline to Week 24 in Hemoglobin A1c (HbA1c) in Patients With Baseline HbA1c ≥9.0% (Last Observation Carried Forward [LOCF])

Secondary endpoints were tested using a sequential testing procedure and are presented in hierarchical order. If no Week 24 assessment was available, HbA1c was recorded from the last postbaseline measurement prior to Week 24. HbA1c was measured as % of hemoglobin by a central laboratory. The population included randomized patients who received treatment and had baseline HbA1c >9.0%. Data after rescue medication were excluded from this analysis. Baseline was defined as the last assessment prior to the start date and time of the first dose of double-blind study drug. In cases where time of the first dose or assessment was not available, baseline was defined as the last assessment on or prior to the date of the first dose of the double-blind study drug. Group 2 (patients with enrollment baseline HbA1c >10% and ≤2%) was considered exploratory, included to obtain initial data. No comparator arm was included. Thus, only key safety and efficacy analyses were performed in Group 2. (NCT00528372)
Timeframe: Baseline to Week 24 (end of Short-term Period)

InterventionPercent (Mean)
Group 1: Dapagliflozin Placebo AM & PM0.19
Group 1: Dapagliflozin, 2.5 mg AM-1.26
Group 1: Dapaglifozon, 5 mg AM-2.00
Group 1: Dapagliflozin, 10 mg AM-2.04
Group 1: Dapagliflozin, 2.5 mg PM-1.35
Group 1: Dapagliflozin, 5 mg PM-1.53
Group 1: Dapagliflozin, 10 mg PM-1.21

Adjusted Mean Change From Baseline to Week 24 in Total Body Weight in Patients With Baseline Body Mass Index ≥27 kg/m^2 (Last Observation Carried Forward)

Secondary endpoints were tested using sequential testing procedure and are presented in hierarchical order. Adjusted mean change from baseline in total body weight at Week 24 (or the last postbaseline measurement prior to Week 24 if no Week 24 assessment was available) was determined. Data after rescue medication was excluded from this analysis. Baseline was defined as the last assessment prior to the start date and time of the first dose of the double-blind study medication. In cases where time of the first dose or time of the assessment was not available, baseline was defined as the last assessment on or prior to the date of the first dose of the double-blind study medication. Group 2 (patients with enrollment baseline HbA1c >10% and ≤2%) was considered an exploratory group, included to obtain initial efficacy and safety data for these patients. No comparator arm was included. Thus, only key safety and efficacy analyses were performed for Group 2. (NCT00528372)
Timeframe: Baseline to Week 24 (end of Short-term Period)

InterventionKilograms (Mean)
Group 1: Dapagliflozin Placebo AM & PM-2.43
Group 1: Dapagliflozin, 2.5 mg AM-3.43
Group 1: Dapagliflozin, 5 mg AM-2.91
Group 1: Dapagliflozin, 10 mg AM-3.39
Group 1: Dapagliflozin, 2.5 mg PM-4.30
Group 1: Dapagliflozin, 5 mg PM-3.70
Group 1: Dapagliflozin, 10 mg PM-3.39

Adjusted Mean Change in Total Body Weight at Week 24 (Last Observation Carried Forward [LOCF]): Group 1

Secondary endpoints were tested using a sequential testing procedure and are presented in hierarchical order. Because the primary focus of the entire dapagliflozin program was on morning dosing in a population with HbA1c ≥7% and ≤10%, only data on AM dosing were summarized. Adjusted mean change from baseline in total body weight at Week 24 (or the last postbaseline measurement prior to Week 24 if no Week 24 assessment was available was determined). Data after rescue medication was excluded from this analysis. Baseline was defined as the last assessment prior to the start date and time of the first dose of the double-blind study medication. In cases where time of the first dose or time of the assessment was not available, baseline was defined as the last assessment on or prior to the date of the first dose of the double-blind study medication. (NCT00528372)
Timeframe: From Baseline to Week 24 (end of Short-term Period)

InterventionKilograms (Mean)
Group 1: Dapagliflozin Placebo AM & PM-2.19
Group 1: Dapagliflozin, 2.5 mg AM-3.25
Group 1: Dapagliflozin, 5 mg AM-2.83
Group 1: Dapagliflozin, 10 mg AM-3.16
Group 1: Dapagliflozin, 2.5 mg PM-3.82
Group 1: Dapagliflozin, 5 mg PM-3.55
Group 1: Dapagliflozin, 10 mg PM-3.05

Adjusted Mean Change in Total Body Weight at Week 24 (Last Observation Carried Forward [LOCF]): Group 2

Secondary endpoints were tested using a sequential testing procedure and are presented in hierarchical order. Adjusted mean change from baseline in total body weight at Week 24 (or the last postbaseline measurement prior to Week 24 if no Week 24 assessment was available was determined). Data after rescue medication was excluded from this analysis. Baseline was defined as the last assessment prior to the start date and time of the first dose of the double-blind study medication. In cases where time of the first dose or time of the assessment was not available, baseline was defined as the last assessment on or prior to the date of the first dose of the double-blind study medication.Group 2 (patients with enrollment baseline HbA1c >10% and ≤2%) was considered an exploratory group, included to obtain initial efficacy and safety data for these patients. No comparator arm was included. (NCT00528372)
Timeframe: From Baseline to Week 24 (end of Short-term Period)

InterventionKilograms (Mean)
Group 2: Dapagliflozin, 5 mg AM-2.06
Group 2: Dapagliflozin, 10 mg AM-1.90

Adjusted Percentage of Participants Achieving a Therapeutic Glycemic Response (Hemoglobin A1c [HbA1c] <7.0%) at Week 24 (Last Observation Carried Forward [LOCF])

Secondary endpoints were tested using a sequential testing procedure and are presented in hierarchical order. Therapeutic glycemic response is defined as HbA1c <7.0%. Data after rescue medication was excluded from this analysis. If no Week 24 assessment was available, HbA1c was recorded from the last postbaseline measurement prior to Week 24. Group 2 (patients with enrollment baseline HbA1c >10% and ≤2%) was considered an exploratory group, included to obtain initial efficacy and safety data for these patients. No comparator arm was included. Thus, only key safety and efficacy analyses were performed for Group 2. (NCT00528372)
Timeframe: Baseline to Week 24 (end of Short-term Period)

InterventionPercentage of participants (Number)
Group 1: Dapagliflozin Placebo AM & PM31.6
Group 1: Dapagliflozin, 2.5 mg AM41.3
Group 1: Dapagliflozin, 5 mg AM44.2
Group 1: Dapagliflozin, 10 mg AM50.8
Group 1: Dapagliflozin, 2.5 mg PM51.4
Group 1: Dapagliflozin, 5 mg PM44.0
Group 1: Dapagliflozin, 10 mg PM51.6

Adjusted Percentage of Participants Who Achieved Hemoglobin A1c [HbA1c] ≤6.5% (Last Observation Carried Forward [LOCF])

Secondary endpoints were tested using a sequential testing procedure and are presented in hierarchical order. If no Week 24 assessment was available, HbA1c was recorded from the last postbaseline measurement prior to Week 24. Data after rescue medication was excluded from this analysis. HbA1c was measured as a percent of hemoglobin. Group 2 (patients with enrollment baseline HbA1c >10% and ≤2%) was considered an exploratory group, included to obtain initial efficacy and safety data for these patients. No comparator arm was included. Thus, only key safety and efficacy analyses were performed for Group 2. (NCT00528372)
Timeframe: Baseline to Week 24 (end of Short-term Period)

InterventionPercentage of participants (Number)
Group 1: Dapagliflozin Placebo AM & PM14.5
Group 1: Dapagliflozin, 2.5 mg AM27.2
Group 1: Dapagliflozin, 5 mg AM26.6
Group 1: Dapagliflozin, 10 mg AM23.1
Group 1: Dapagliflozin, 2.5 mg PM33.4
Group 1: Dapagliflozin, 5 mg PM25.8
Group 1: Dapagliflozin, 10 mg PM26.0

Number of Participants With Adverse Events (AE), Hypoglycemia, Related AEs, Death as Outcome, Related Serious AEs (SAEs), SAEs and AEs Leading to Discontinuation, and Hypoglycemia Leading to Discontinuation (Short-term + Long-term Periods)

AE=any new unfavorable symptom, sign, or disease or worsening of a preexisting condition that may not have a causal relationship with treatment. SAE=a medical event that at any dose results in death, persistent or significant disability/incapacity, or drug dependency/abuse; is life-threatening, an important medical event, or a congenital anomaly/birth defect; or requires or prolongs hospitalization. Related=having certain, probable, possible, or missing relationship to study drug. Includes non-SAEs and hypoglycemia with onset on or after the first date/time of double-blind treatment and on or prior to the last day of short-term plus long-term treatment plus 4 days. Includes SAEs with onset on or after the first date/time of double-blind treatment and on or prior to the last day of short-term plus long-term treatment plus 30 days. (NCT00528372)
Timeframe: Day 1 to Week 102 (end of Long-term Period) + 30 days

,,,,,,,,
InterventionParticipants (Number)
>=1 AE>=1 Hypoglycemia>=1 Related AEsDeathsSAEs>=1 related SAESAEs leading to discontinuationAE leading to discontinuationHypoglycemia leading to discontinuation
Group 1: Dapagliflozin Placebo, AM & PM58415050140
Group 1: Dapagliflozin, 10 mg AM56317110050
Group 1: Dapagliflozin, 10 mg PM54221030170
Group 1: Dapagliflozin, 2.5 mg AM48313060040
Group 1: Dapagliflozin, 2.5 mg PM50219170120
Group 1: Dapagliflozin, 5 mg AM43010040140
Group 1: Dapagliflozin, 5 mg PM50018150260
Group 2: Dapagliflozin, 10 mg AM33110000010
Group 2: Dapagliflozin, 5 mg AM29112010000

Number of Participants With Changes From Baseline in Electrocardiogram (ECG) Findings (Last Observation Carried Forward {LOCF])

12-Lead ECGs were performed at entry into lead-in period Day -7 visit and Week 24/end of treatment visit (LOCF) on participants who were supine. ECGs were assessed by the investigator. Baseline was Day -7 for this parameter, and data after rescue were included.The Week 102 value is the last observation, regardless of rescue prior to Week 102 if no Week 102 measurement was available. Group 2 (patients with enrollment baseline HbA1c >10% and ≤2%) was considered an exploratory group, included to obtain initial efficacy and safety data for these patients. No comparator arm was included. Thus, only key safety and efficacy analyses were performed for Group 2. (NCT00528372)
Timeframe: Baseline to Week 24 (end of Short-term Period)

,,,,,,
InterventionParticipants (Number)
Baseline: Normal/Week 24: NormalBaseline: Normal/Week 24: AbnormalBaseline: Normal/Week 24: Not reportedBaseline: Abnormal/Week 24: NormalBaseline: Abnormal/Week 24: AbnormalBaseline: Abnormal/Week 24: Not reportedBaseline: Not reported/Week 24: NormalBasline: Not reported/Week 24: AbnormalBaseline: Not reported/Week 24: Not reported
Group 1: Dapagliflozin Placebo AM & PM38605180008
Group 1: Dapagliflozin, 10 mg AM311061700015
Group 1: Dapagliflozin, 10 mg PM35100101100010
Group 1: Dapagliflozin, 2.5 mg AM36302170007
Group 1: Dapagliflozin, 2.5 mg PM333041700010
Group 1: Dapagliflozin, 5 mg AM325031100013
Group 1: Dapagliflozin, 5 mg PM336041400011

Number of Participants With Elevated Levels of Liver Enzymes on Laboratory Test Results (Short-term and Long-term Periods)

Data after rescue was included. AST=aspartate aminotransferase; ALT=alanine aminotransferase; ALP=alkaline phosphatase. Group 2 (patients with enrollment baseline HbA1c >10% and ≤2%) was considered an exploratory group, included to obtain initial efficacy and safety data for these patients. No comparator arm was included. Thus, only key safety and efficacy analyses were performed for Group 2. (NCT00528372)
Timeframe: Day 1 to Week 102 (end of Long-term Period)

,,,,,,
InterventionParticipants (Number)
AST >3*ULN (n=75, 65, 62, 70, 67, 67, 74, 34, 37))AST >5*ULN (n=75, 65, 62, 70, 67, 67, 74)ALT >3*ULN (n=75, 65, 62, 70, 67, 67, 74)ALT >5*ULN (n=75, 65, 62, 70, 67, 67, 74)Bilirubin >1.5 ULN (n=75, 65, 62, 70, 67, 67, 74)Bilirubin >2*ULN (n=75, 65, 62, 70, 67, 67, 74)ALP >1.5*ULN (n=75, 65, 62, 70, 67, 67, 74)
Group 1: Dapagliflozin Placebo AM & PM0010204
Group 1: Dapagliflozin, 10 mg AM0010001
Group 1: Dapagliflozin, 10 mg PM4000002
Group 1: Dapagliflozin, 2.5 mg AM1011003
Group 1: Dapagliflozin, 2.5 mg PM5200214
Group 1: Dapagliflozin, 5 mg AM1020101
Group 1: Dapagliflozin, 5 mg PM1000103

Number of Participants With Laboratory Test Results Meeting the Criteria for Marked Laboratory Abnormality (Short-term and Long-term Periods)

Baseline was defined as the last assessment prior to the start of the first dose of the double-blind study medication. Data included from baseline up to and including the last day of treatment plus 4 days. Data after rescue were also included. ULN=upper limit of normal; preRX=pretreatment. Phosphorus, inorganic (high) defined as >=5.6 mg/dL for ages 17-65 years or >=5.1 mg/dL for ages >=66. (NCT00528372)
Timeframe: Baseline to Week 102 (end of Long-term Period)

,,,,,,,,
InterventionParticipants (Number)
Hematocrit (>55%)Hematocrit (>60%)Hemoglobin (>18 g/dL)Glucose ( >350 mg/dL)Glucose (<54 mg/dL)Creatine kinase (>5*ULN)Creatine kinase (>10*ULN)Calcium, total (<7.5 mg/dL)Bicarbonate (<=13 mEq/L)Potassium, serum (>=6 mEqL)Sodium, serum (<130 mEq/L)Sodium, serum (>150 mEq/L)Phosphorus, inorganic (high)Albumin/creatinine ratio (>1800 mg/g)Creatinine (>=1.5 preRX creatinine)
Group 1: Dapagliflozin Placebo000201030311200
Group 1: Dapagliflozin, 10 mg AM214001100200001
Group 1: Dapagliflozin, 10 mg PM416002110110201
Group 1: Dapagliflozin, 2.5 mg AM103200000121011
Group 1: Dapagliflozin, 2.5 mg PM202021130401001
Group 1: Dapagliflozin, 5 mg AM002000001100102
Group 1: Dapagliflozin, 5 mg PM101001120100301
Group 2: Dapagliflozin, 10 mg AM415000000110201
Group 2: Dapagliflozin, 5 mg AM203000000100001

Adjusted Mean Change From Baseline in A1C Levels (Last Observation Carried Forward [LOCF])

Change from baseline: post-pre. Adjusted for baseline (value and metformin use). ANCOVA model: difference between week t and baseline values=baseline values + treatment + metformin use (NCT00757588)
Timeframe: Baseline to Week 24

InterventionPercentage of change (Mean)
Saxagliptin, 5 mg + Insulin-0.73
Placebo + Insulin-0.32

Change From Baseline in 120-minute PPG Values During an MTT

An MTT is a 2-part test that measures glucose and insulin levels after an overnight fast and before ingesting a meal consisting of a nutritional drink and power bar and again at prespecified times (30, 60, 120, and 180 minutes) after the start of ingestion of the meal. (NCT00757588)
Timeframe: Baseline to Week 24

Interventionmg/dL (Mean)
Saxagliptin, 5 mg + Insulin-27.2
Placebo + Insulin-4.2

Change From Baseline in Fasting Plasma Glucose Values

(NCT00757588)
Timeframe: Baseline to Week 24

Interventionmg/dL (Mean)
Saxagliptin, 5 mg + Insulin-10.1
Placebo + Insulin-6.1

Change From Baseline in Mean Total Daily Dose of Insulin (MTDDI) (LOCF)

Based on information recorded in the participant's daily diary. The MTDDI was calculated at every visit using the values patients recorded since the last regularly scheduled visit (minimum of 80% of days with a value). At every visit, the MTDDI was compared with the participant's baseline MTDDI (measured during a 4-week lead-in period) to identify any changes in insulin use at that visit compared with insulin use at baseline. (NCT00757588)
Timeframe: Baseline to Week 24

InterventionUnits (Mean)
Saxagliptin, 5 mg + Insulin1.71
Placebo + Insulin5.01

Change From Baseline in Postprandial Glucose (PPG) Area Under the Curve (AUC) Response to an Meal Tolerance Test (MTT)

An MTT is a 2-part test that measures glucose and insulin levels after an overnight fast and before ingesting a meal consisting of a nutritional drink and power bar and again at prespecified times (30, 60, 120, and 180 minutes) after the start of ingestion of the meal (NCT00757588)
Timeframe: Baseline to Week 24

Interventionmg*min/dL (Mean)
Saxagliptin, 5 mg + Insulin-4548.5
Placebo + Insulin-718.8

Number of Participants With Abnormal Changes From Baseline in Electrocardiogram (ECG) Results

"ECG abnormalities included those in nonspecific other categories (Other nonspecific ST/T, Other intraventricular conduction defect, Other, and Other rhythm abnormalities)and nonspecific findings, such as sinus bradycardia, sinus arrythmia, sinus tachycardia, poor R-wave progression, and ventricular premature contractions." (NCT00757588)
Timeframe: Baseline to Week 52

InterventionParticipants (Number)
Saxagliptin, 5 mg + Insulin15
Placebo + Insulin11

Percentage of Participants Achieving a Therapeutic Glycemic Response

Therapeutic glycemic response is defined as an A1C<7%. Significance was not interpreted with a p value. (NCT00757588)
Timeframe: Baseline to Week 24

InterventionPercentage of participants (Number)
Saxagliptin, 5 mg + Insulin17.3
Placebo + Insulin6.7

Mean Changes From Baseline in Heart Rate

(NCT00757588)
Timeframe: Baseline to Weeks 2, 4, 6, 8, 12, 16, 20, 24, 28, 36, 44, and 52

,
InterventionBeats per minute (Number)
Week 2 (n=294, 147)Week 4 (n=293, 144)Week 6 (n=280, 141)Week 8 (n=290, 142)Week 12 (n=286, 144)Week 16 (n=278, 139)Week 20 (n=276, 137)Week 24 (n=273, 134)Week 28 (n=264, 132)Week 36 (n=261, 129)Week 44 (n=250, 125)Week 52 (n=246, 125)
Placebo + Insulin-0.7-1.0-0.9-0.70.2-0.60.4-1.0-0.6-0.0-0.70.2
Saxagliptin, 5 mg + Insulin-0.5-0.5-0.5-0.00.3-1.0-0.50.0-1.00.00.2-0.3

Mean Changes From Baseline in Systolic and Diastolic Blood Pressure Readings

(NCT00757588)
Timeframe: Baseline to Weeks 2, 4, 6, 8, 12, 16, 20, 24, 28, 36, 44, and 52

,
Interventionmm Hg (Number)
Systolic blood pressure (Week 2) (n=294, 147)Systolic blood pressure (Week 4) (n=293, 144)Systolic blood pressure (Week 6) (n=280, 141)Systolic blood pressure (Week 8) (n=290, 142)Systolic blood pressure (Week 12) (n=286, 144)Systolic blood pressure (Week 16) (n=278, 139)Systolic blood pressure (Week 20) (n=276, 137)Systolic blood pressure (Week 24) (n=273, 134)Systolic blood pressure (Week 28) (n=264, 132)Systolic blood pressure (Week 36) (n=261, 129)Systolic blood pressure (Week 44) (n=250, 125)Systolic blood pressure (Week 52) (n=246, 125)Diastolic blood pressure (Week 2) (n=294, 147)Diastolic blood pressure (Week 4) (n=293, 144)Diastolic blood pressure (Week 6) (n=280, 141)Diastolic blood pressure (Week 8) (n=290, 142)Diastolic blood pressure (Week 12) (n=286, 144)Diastolic blood pressure (Week 16) (n=278, 139)Diastolic blood pressure (Week 20) (n=276, 137)Diastolic blood pressure (Week 24) (n=273, 134)Diastolic blood pressure (Week 28) (n=264, 132)Diastolic blood pressure (Week 36) (n=261, 129)Diastolic blood pressure (Week 44) (n=250, 125)Diastolic blood pressure (Week 52) (n=246, 125)
Placebo + Insulin2.30.01.02.42.21.11.3-0.11.83.62.61.01.41.80.32.11.01.31.10.50.20.20.40.1
Saxagliptin, 5 mg + Insulin-1.0-1.2-0.8-0.8-1.7-1.2-0.6-1.5-1.4-0.7-0.60.00.10.00.0-0.5-0.8-1.1-0.7-1.7-1.6-1.2-0.3-0.5

Number of Participants With at Least 1 Adverse Event (AE), at Least 1 Treatment-related AE, Death as Outcome, at Least 1 Serious Adverse Event (SAE), at Least 1 Treatment-related SAE, Discontinuations Due to SAEs, and Discontinuations Due to AEs

An AE is any new untoward medical occurrence or worsening of a preexisting medical condition that does not necessarily have a causal relationship with this treatment. An SAE is any untoward medical event that at any dose: results in death, persistent or significant disability/incapacity, or drug dependency or abuse; is life-threatening, an important medical event, or a congenital anomaly/birth defect; requires inpatient hospitalization; or prolongs existing hospitalization. Treatment-related=possibly, probably, or certainly related to and of unknown relationship to study treatment. (NCT00757588)
Timeframe: Baseline to Week 52, continuously

,
InterventionParticipants (Number)
At least 1 AEAt least 1 treatment-related AEDeathsAt least 1 SAEAt least 1 treatment-related SAEDiscontinuations due to SAEsDiscontinuations due to AEs
Placebo + Insulin10834013003
Saxagliptin, 5 mg + Insulin20256225349

Number of Participants With Marked Laboratory Abnormalities During the 24-Week ST + 52-Week LT Treatment Period

"Marked abnormality=a laboratory value lying outside the predefined criteria and more extreme (farther from the limit)on-treatment than at baseline. ULN=upper limit of normal; LLN=lower limit of normal; prx=pre-RX=pretreatment.~Criteria 1: if prx=0 use >=2, if prx=0.5 or 1 use >=3, if prx=2 use 4." (NCT00757588)
Timeframe: Baseline and during and up to 14 days after last dose of study drug (in Week 52)

,
InterventionParticipants (Number)
Hemoglobin <8 g/dL (n=300; 150)Hematocrit <0.75*prx (n=300; 150)Platelets <50*10^9 c/L (n=297; 145)Platelets >1.5*ULN (n=297; 145)Leukocytes <2*1000 c/uL (n=300; 150)Neutrophils <1*1000 c/uL (n=296; 150)Eosinophils >0.9*1000 c/uL (n=296; 150)Lymphocytes <=0.75*1000 c/uL (n=296; 150)Alkaline phosphatase >3*prx & >ULN (n=302; 150)Alkaline phosphatase >1.5 ULN (n=302; 150)Aspartate aminotransferase >3* ULN (n=298; 148)Aspartate aminotransferase>5* ULN (n=298; 148)Aspartate aminotransferase >10*ULN (n=298; 148)Aspartate aminotransferase >20*ULN (n=298; 148)Alanine transaminase >3*ULN (n=300; 148)Alanine transaminase >5*ULN (n=300; 148)Alanine transaminase >10*ULN (n=300; 148)Alanine transaminase >20*ULN (n=300; 148)Bilirubin, total >2 mg/dL (n=301; 150)Bilirubin, total >1.5*ULN (n=301; 150)Bilirubin, total >2*ULN (n=301; 150)Blood urea nitrogen >2*prx & >ULN (n=302; 150)Creatinine >2.5 mg/dL (n=303; 150)Glucose, serum fasting <50 mg/dL (n=0; 0)Glucose, serum fasting >500 mg/dL (n=0; 0)Glucose, serum unspecified <50 mg/dL (n=0; 0)Glucose, serum unspecified >500 mg/dL (n=0; 0)Glucose, plasma fasting <50 mg/dL (n=301;150)Glucose, plasma fasting >500 mg/dL (n=301;150)Glucose, plasma unspecified <50 mg/dL (n=272; 133)Glucose, plasma unspecified >500 mg/d (n=272; 133)Sodium, serum <0.9*prx & <=130 mEq/L (n=302; 150)Sodium, serum >1.1*prx & >=150 mEq/L (n=302; 150)Potassium, serum <0.8 prx &<=3.2 mEq/L(n=300; 148)Potassium, serum >1.2*prx&>= 6.0 mEq/L(n=300; 148)Chloride, serum <90 mEq/L (n=302; 150)Chloride, serum >120 mEq/L (n=302; 150)Albumin <0.9*LLN; if prxCreatine kinase >5*ULN (n=301, 148)Uric acid >1.5*ULN; if prx >ULN, >2 (n=0,0)Protein urine (see criteria 1) (n=297,146)Blood urine (see criteria 1) (n=297; 146)Red blood cells urine (see criteria 1) (n=53; 31)White blood cells urine (see criteria 1)(n=115;53)
Placebo + Insulin020010721500003000010700000011100180002032310
Saxagliptin, 5 mg + Insulin22000193210210051000005000005051103810160814835

Percentage of Participants With Reported and Confirmed Hypoglycemia

Confirmed hypoglycemia=fingerstick glucose measurement of ≤50 mg/dL with associated symptoms/ (NCT00757588)
Timeframe: Baseline to Week 52

,
InterventionPercentage of Participants (Number)
ReportedConfirmed
Placebo + Insulin24.56.6
Saxagliptin, 5 mg + Insulin19.47.6

Shift in Absolute Lymphocyte Counts From Baseline to Selected Visits (LOCF)

Absolute lymphocyte count=value*10^3 c/uL (NCT00757588)
Timeframe: Baseline and Weeks 24 and 52

,
InterventionParticipants (Number)
Baseline <= 0.75; Week 24 <= 0.75Baseline <= 0.75; Week 24 >0.75- <= 5.00Baseline <= 0.75; Week 24 >5.00Baseline >0.75- <= 5.00; Week 24 <= 0.75Baseline >0.75- <= 5.00; Week 24 >0.75- <= 5.00Baseline >0.75- <= 5.00; Week 24 >5.00Baseline >5.00; Week 24 <= 0.75Baseline >5.00; Week 24 >0.75- <= 5.00Baseline >5.00; Week 24 >5.00Baseline <= 0.75; Week 52 <= 0.75Baseline <= 0.75; Week 52 >0.75- <= 5.00Baseline <= 0.75; Week 52 >5.00Baseline >0.75- <= 5.00; Week 52 <= 0.75Baseline >0.75- <= 5.00; Week 52 >0.75- <= 5.00Baseline >0.75- <= 5.00; Week 52 >5.00Baseline >5.00; Week 52 <= 0.75Baseline >5.00; Week 52 >0.75- <= 5.00Baseline >5.00; Week 52 >5.00
Placebo + Insulin0200148000002001471000
Saxagliptin, 5 mg + Insulin0001293100100002950001

Shift in Platelet Counts From Baseline to Selected Visits (LOCF)

Platelet count=value*10^9 c/L (NCT00757588)
Timeframe: Baseline and Weeks 24 and 52

,
InterventionParticipants (Number)
Baseline <= 100; Week 24 <= 100Baseline <= 100; Week 24 >100 - <= 600Baseline <= 100; Week 24 >600Baseline >100 - <= 600; Week 24 <= 100Baseline >100 - <= 600; Week 24 >100 - <= 600Baseline >100 - <= 600; Week 24 >600Baseline >600; Week 24 <= 100Baseline >600; Week 24 >100 - <= 600Baseline >600; Week 24 >600Baseline <= 100; Week 52 <= 100Baseline <= 100; Week 52 >100 - <= 600Baseline <= 100; Week 52 >600Baseline >100 - <= 600; Week 52 <= 100Baseline >100 - <= 600; Week 52 >100 - <= 600Baseline >100 - <= 600; Week 52 >600Baseline >600; Week 52 <= 100Baseline >600; Week 52 >100 - <= 600Baseline >600; Week 52 >600
Placebo + Insulin0001143000001001440000
Saxagliptin, 5 mg + Insulin0001296000000022950000

Mean Slope of the Regressions of Change From Week 24 to Week 104 in HbA1c

Mean slopes of regression of change from Week 24 to Week 104 in HbA1c for saxagliptin added on to metformin versus glipizide added on to metformin (Full Analysis Set) achieved by fitting a mixed model with subject specific slopes for the time effect (weeks on randomized treatment was utilized). This analysis gives an assessment of the durability of the HbA1c effect. (NCT00575588)
Timeframe: Week 24 to Week 104

InterventionPercent (Mean)
Saxagliptin + Metformin0.0041
Glipizide + Metformin0.0076

Mean Slope of the Regressions of Change From Week 24 to Week 52 in HbA1c

Mean slopes of regression of change from Week 24 to Week 52 in HbA1c for saxagliptin added on to metformin versus glipizide added on to metformin (Per Protocol Analysis Set) achieved by fitting a mixed model with subject specific slopes for the time effect (weeks on randomized treatment was utilized). This analysis gives an assessment of the durability of the HbA1c effect. (NCT00575588)
Timeframe: Week 24 to Week 52

InterventionPercent (Mean)
Saxagliptin + Metformin0.001
Glipizide + Metformin0.004

Proportion of Participants Reporting at Least One Episode of Any Hypoglycaemic Event Over 104 Weeks

Proportion of participants reporting at least one episode of any hypoglycaemic event for saxagliptin added on to metformin versus glipizide added on to metformin over 104 weeks (Safety Analysis Set) (NCT00575588)
Timeframe: Baseline, Week 104

InterventionPercentage of Participants (Number)
Saxagliptin + Metformin3.5
Glipizide + Metformin38.4

Proportion of Participants Reporting at Least One Episode of Any Hypoglycaemic Event Over 52 Weeks

Proportion of participants reporting at least one episode of any hypoglycaemic event for saxagliptin added on to metformin versus glipizide added on to metformin over 52 weeks (Safety Analysis Set) (NCT00575588)
Timeframe: From Baseline to Week 52

InterventionPercentage of Participants (Number)
Saxagliptin + Metformin3
Glipizide + Metformin36.3

Body Weight Change From Baseline to Week 104

Adjusted mean change from baseline in Body Weight achieved with saxagliptin added on to metformin versus glipizide added on to metformin at Week 104. Body Weight is a continuous measure, the change from baseline for each participant is calculated as the Week 104 value minus the baseline value. (NCT00575588)
Timeframe: Baseline, Week 104

,
Interventionkilograms (Mean)
BaselineWeek 104Adjusted Change from Baseline to Week 104
Glipizide + Metformin88.5789.801.29
Saxagliptin + Metformin88.6987.47-1.47

Body Weight Change From Baseline to Week 52

Adjusted mean change from baseline in Body Weight achieved with saxagliptin added on to metformin versus glipizide added on to metformin at Week 52 (Safety Analysis Set). Body Weight is a continuous measure, the change from baseline for each participant is calculated as the Week 52 (LOCF) value minus the baseline value. (NCT00575588)
Timeframe: Baseline, Week 52 (Last Observation Carried Forward)

,
Interventionkilogram (Mean)
BaselineWeek 52Adjusted Change from Baseline to Week 52
Glipizide + Metformin88.689.71.1
Saxagliptin + Metformin88.787.6-1.1

Hemoglobin A1c (HbA1c) Change From Baseline to Week 104

Adjusted mean change from baseline in HbA1c achieved with saxagliptin added on to metformin versus glipizide added on to metformin at Week 104 (Full Analysis Set). HbA1c is a continuous measure, the change from baseline for each participant is calculated as the Week 104 value minus the baseline value. (NCT00575588)
Timeframe: Baseline, Week 104

,
InterventionPercent (Mean)
BaselineWeek 104Adjusted Change from Baseline to Week 104
Glipizide + Metformin7.657.27-0.35
Saxagliptin + Metformin7.657.27-0.41

Hemoglobin A1c (HbA1c) Change From Baseline to Week 52

Adjusted mean change from baseline in HbA1c achieved with saxagliptin added on to metformin versus glipizide added on to metformin at Week 52 (Per Protocol Analysis Set). HbA1c is a continuous measure, the change from baseline for each participant is calculated as the Week 52 value minus the baseline value. (NCT00575588)
Timeframe: Baseline to 52 Weeks

,
InterventionPercent (Mean)
BaselineWeek 52Adjusted Change from Baseline to Week 52
Glipizide + Metformin7.536.71-0.80
Saxagliptin + Metformin7.466.74-0.74

Percentage of Participants Achieving A1C < 7% at Week 24, Saxagliptin Plus Metformin Versus Metformin Monotherapy

Percentage of participants achieving A1C < 7%, the American Diabetes Association's defined goal for glycemia, at each dose of saxagliptin plus metformin versus metformin alone at Week 24. (NCT00327015)
Timeframe: Week 24

InterventionPercentage of participants (Number)
Saxagliptin 5 mg + Metformin60.3
Saxagliptin 10 mg + Metformin59.7
Metformin41.1

Percentage of Participants Achieving A1C < 7% at Week 24, Saxagliptin Plus Metformin Versus Saxagliptin Monotherapy

Percentage of participants achieving A1C < 7%, the American Diabetes Association's defined goal for glycemia, at each dose of saxagliptin plus metformin versus saxagliptin alone at Week 24. (NCT00327015)
Timeframe: Week 24

InterventionPercentage of participants (Number)
Saxagliptin 5 mg + Metformin60.3
Saxagliptin 10 mg + Metformin59.7
Saxagliptin 10 mg32.2

Percentage of Participants Achieving A1C ≤6.5% at Week 24, Saxagliptin Plus Metformin Versus Metformin Monotherapy

Percentage of participants achieving A1C ≤6.5%, at each dose of saxagliptin plus metformin versus metformin alone at Week 24. (NCT00327015)
Timeframe: Week 24

InterventionPercentage of participants (Number)
Saxagliptin 5 mg + Metformin45.3
Saxagliptin 10 mg + Metformin40.6
Metformin29.0

Percentage of Participants Achieving A1C ≤6.5% at Week 24, Saxagliptin Plus Metformin Versus Saxagliptin Monotherapy

Percentage of participants achieving A1C ≤6.5%, at each dose of saxagliptin plus metformin versus saxagliptin alone at Week 24. (NCT00327015)
Timeframe: Week 24

InterventionPercentage of Participants (Number)
Saxagliptin 5 mg + Metformin45.3
Saxagliptin 10 mg + Metformin40.6
Saxagliptin 10 mg20.3

Percentage of Participants Requiring Rescue or Discontinuation at Week 24, Saxagliptin Plus Metformin Versus Metformin Monotherapy

Percentage of participants requiring rescue for failing to achieve pre-specified glycemic targets or discontinuing for lack of efficacy within the 24-week treatment period at each dose of saxagliptin plus metformin versus metformin alone. (NCT00327015)
Timeframe: Week 24

InterventionPercentage of participants (Number)
Saxagliptin 5 mg + Metformin7.5
Saxagliptin 10 mg + Metformin5.9
Metformin10.1

Percentage of Participants Requiring Rescue or Discontinuation at Week 24, Saxagliptin Plus Metformin Versus Saxagliptin Monotherapy

Percentage of participants requiring rescue for failing to achieve pre-specified glycemic targets or discontinuing for lack of efficacy within the 24-week treatment period at each dose of saxagliptin plus metformin versus saxagliptin alone. (NCT00327015)
Timeframe: Week 24

InterventionPercentage of participants (Number)
Saxagliptin 5 mg + Metformin7.5
Saxagliptin 10 mg + Metformin5.9
Saxagliptin 10 mg21.2

Change From Baseline in A1C at Week 24, Saxagliptin Plus Metformin Versus Metformin Monotherapy

Mean change from baseline in A1C at Week 24, adjusted for baseline value. (NCT00327015)
Timeframe: Baseline, Week 24

,,
Interventionpercent (Mean)
Baseline MeanWeek 24 MeanAdjusted Mean Change from Baseline
Metformin9.437.48-1.99
Saxagliptin 10 mg + Metformin9.537.02-2.49
Saxagliptin 5 mg + Metformin9.416.93-2.53

Change From Baseline in Fasting Plasma Glucose (FPG) at Week 24, Saxagliptin Plus Metformin Versus Metformin Monotherapy

Mean change from baseline in FPG at Week 24, adjusted for baseline value. (NCT00327015)
Timeframe: Baseline, Week 24

,,
Interventionmg/dL (Mean)
Baseline MeanWeek 24 MeanAdjusted Mean Change from Baseline
Metformin199.1152.7-47.3
Saxagliptin 10 mg + Metformin204.3140.1-62.2
Saxagliptin 5 mg + Metformin198.9140.2-59.8

Change From Baseline in Fasting Plasma Glucose (FPG) at Week 24, Saxagliptin Plus Metformin Versus Saxagliptin Monotherapy

Mean change from baseline in FPG at Week 24, adjusted for baseline value. (NCT00327015)
Timeframe: Baseline, Week 24

,,
Interventionmg/dL (Mean)
Baseline MeanWeek 24 MeanAdjusted Mean Change from Baseline
Saxagliptin 10 mg200.9169.9-30.9
Saxagliptin 10 mg + Metformin204.3140.1-62.2
Saxagliptin 5 mg + Metformin198.9140.2-59.8

Change From Baseline in Hemoglobin A1c (A1C) at Week 24, Saxagliptin Plus Metformin Versus Saxagliptin Monotherapy

Mean change from baseline in A1C at Week 24, adjusted for baseline value. (NCT00327015)
Timeframe: Baseline, Week 24

,,
Interventionpercent (Mean)
Baseline MeanWeek 24 MeanAdjusted Mean Change from Baseline
Saxagliptin 10 mg9.617.86-1.69
Saxagliptin 10 mg + Metformin9.537.02-2.49
Saxagliptin 5 mg + Metformin9.416.93-2.53

Changes From Baseline in Postprandial Glucose (PPG) Area Under the Curve (AUC) Response to an Oral Glucose Tolerance Test (OGTT) at Week 24, Saxagliptin Plus Metformin Versus Metformin Monotherapy

Mean change from baseline for 0 to 180 minutes PPG AUC at Week 24, adjsuted for baseline value. (NCT00327015)
Timeframe: Baseline, Week 24

,,
Interventionmg*min/dL (Mean)
Baseline MeanWeek 24 MeanAdjusted Mean Change from Baseline
Metformin5793742428-15005
Saxagliptin 10 mg + Metformin5721935790-21336
Saxagliptin 5 mg + Metformin5553135324-21080

Changes From Baseline in Postprandial Glucose (PPG) Area Under the Curve (AUC) Response to an Oral Glucose Tolerance Test (OGTT) at Week 24, Saxagliptin Plus Metformin Versus Saxagliptin Monotherapy

Mean change from baseline for 0 to 180 minutes PPG AUC at Week 24, adjusted for baseline value. (NCT00327015)
Timeframe: Baseline, Week 24

,,
Interventionmg*min/dL (Mean)
Baseline MeanWeek 24 MeanAdjusted Mean Change from Baseline
Saxagliptin 10 mg5758441229-16054
Saxagliptin 10 mg + Metformin5721935790-21336
Saxagliptin 5 mg + Metformin5553135324-21080

Adjusted Mean Change From Baseline in FPG

To compare the change from baseline in fasting plasma glucose (FPG) to week 24 (LOCF) between dapagliflozin and placebo (NCT01392677)
Timeframe: Baseline to week 24

Interventionmg/dL (Least Squares Mean)
Placebo Plus Metformin Plus Sulfonylurea-0.78
Dapagliflozin 10mg Plus Metformin Plus Sulfonylurea-34.23

Adjusted Mean Change From Baseline in HbA1c Levels

To compare the change from baseline in HbA1c to week 24 between dapagliflozin 10 mg in combination with metformin and sulfonylurea and placebo in combination with metformin and sulfonylurea. (NCT01392677)
Timeframe: Baseline to week 24

InterventionPercent (Least Squares Mean)
Placebo Plus Metformin Plus Sulfonylurea-0.17
Dapagliflozin 10mg Plus Metformin Plus Sulfonylurea-0.86

Adjusted Mean Change From Baseline in Seated Systolic Blood Pressure

To compare the change from baseline in seated systolic blood pressure (SBP) to week 8 (LOCF) between dapagliflozin and placebo (NCT01392677)
Timeframe: Baseline to week 8

InterventionmmHg (Least Squares Mean)
Placebo Plus Metformin Plus Sulfonylurea-0.27
Dapagliflozin 10mg Plus Metformin Plus Sulfonylurea-4.04

Adjusted Mean Change From Baseline in Total Body Weight

To compare the change from baseline in total body weight to week 24 (LOCF) between dapagliflozin and placebo (NCT01392677)
Timeframe: Baseline to week 24

Interventionkg (Least Squares Mean)
Placebo Plus Metformin Plus Sulfonylurea-0.58
Dapagliflozin 10mg Plus Metformin Plus Sulfonylurea-2.65

Proportion of Participants With HbA1c Value < 7.0% at Week 24 (LOCF)

To compare the proportion of subjects achieving a therapeutic glycemic response, defined as HbA1c <7.0%, at week 24 (LOCF) between dapagliflozin and placebo (NCT01392677)
Timeframe: Baseline to week 24

InterventionPercentage of participants (Least Squares Mean)
Placebo Plus Metformin Plus Sulfonylurea11.1
Dapagliflozin 10mg Plus Metformin Plus Sulfonylurea31.8

Baseline Body Weight

(NCT01059825)
Timeframe: Baseline

Interventionkg (Mean)
Placebo83.78
Ertugliflozin 1 mg83.44
Ertugliflozin 5 mg85.74
Ertugliflozin 10 mg82.28
Ertugliflozin 25 mg81.81
Sitagliptin 100 mg85.52

Baseline Diastolic Blood Pressure

Sitting blood pressure was measured in triplicate and the average of the measurements taken at a single assessment time was analyzed. (NCT01059825)
Timeframe: Baseline

InterventionmmHg (Mean)
Placebo79.14
Ertugliflozin 1 mg78.95
Ertugliflozin 5 mg78.19
Ertugliflozin 10 mg78.45
Ertugliflozin 25 mg78.61
Sitagliptin 100 mg79.15

Baseline Fasting Plasma Glucose

Laboratory measurements were performed after an overnight fast ≥8 hours in duration. (NCT01059825)
Timeframe: Baseline

Interventionmg/dL (Mean)
Placebo165.3
Ertugliflozin 1 mg162.5
Ertugliflozin 5 mg156.5
Ertugliflozin 10 mg163.3
Ertugliflozin 25 mg171.3
Sitagliptin 100 mg166.2

Baseline Hemoglobin A1c (HbA1c)

HbA1c is measured as percent. (NCT01059825)
Timeframe: Baseline

InterventionPercent (Mean)
Placebo8.08
Ertugliflozin 1 mg8.01
Ertugliflozin 5 mg7.88
Ertugliflozin 10 mg8.13
Ertugliflozin 25 mg8.30
Sitagliptin 100 mg8.24

Baseline Systolic Blood Pressure

Sitting blood pressure was measured in triplicate and the average of the measurements taken at a single assessment time was analyzed. (NCT01059825)
Timeframe: Baseline

InterventionmmHg (Mean)
Placebo126.7
Ertugliflozin 1 mg126.5
Ertugliflozin 5 mg127.9
Ertugliflozin 10 mg125.8
Ertugliflozin 25 mg124.9
Sitagliptin 100 mg126.6

Change From Baseline in Diastolic Blood Pressure at Week 12

Sitting blood pressure was measured in triplicate and the average of the measurements taken at a single assessment time was analyzed. The change from baseline is the Week 12 diastolic blood pressure minus the Week 0 diastolic blood pressure (LOCF). (NCT01059825)
Timeframe: Baseline and Week 12

InterventionmmHg (Least Squares Mean)
Placebo0.81
Ertugliflozin 1 mg-1.12
Ertugliflozin 5 mg-1.01
Ertugliflozin 10 mg-3.18
Ertugliflozin 25 mg-1.83
Sitagliptin 100 mg1.68

Change From Baseline in Diastolic Blood Pressure at Week 2

Sitting blood pressure was measured in triplicate and the average of the measurements taken at a single assessment time was analyzed. The change from baseline is the Week 2 diastolic blood pressure minus the Week 0 diastolic blood pressure (LOCF). (NCT01059825)
Timeframe: Baseline and Week 2

InterventionmmHg (Least Squares Mean)
Placebo-0.57
Ertugliflozin 1 mg-1.25
Ertugliflozin 5 mg-1.26
Ertugliflozin 10 mg-1.97
Ertugliflozin 25 mg-3.01
Sitagliptin 100 mg0.92

Change From Baseline in Diastolic Blood Pressure at Week 4

Sitting blood pressure was measured in triplicate and the average of the measurements taken at a single assessment time was analyzed. The change from baseline is the Week 4 diastolic blood pressure minus the Week 0 diastolic blood pressure (LOCF). (NCT01059825)
Timeframe: Baseline and Week 4

InterventionmmHg (Least Squares Mean)
Placebo-0.80
Ertugliflozin 1 mg-2.47
Ertugliflozin 5 mg-3.08
Ertugliflozin 10 mg-2.81
Ertugliflozin 25 mg-2.10
Sitagliptin 100 mg-0.51

Change From Baseline in Diastolic Blood Pressure at Week 8

Sitting blood pressure was measured in triplicate and the average of the measurements taken at a single assessment time was analyzed. The change from baseline is the Week 8 diastolic blood pressure minus the Week 0 diastolic blood pressure (LOCF). (NCT01059825)
Timeframe: Baseline and Week 8

InterventionmmHg (Least Squares Mean)
Placebo0.80
Ertugliflozin 1 mg-1.40
Ertugliflozin 5 mg-0.69
Ertugliflozin 10 mg-2.23
Ertugliflozin 25 mg-1.20
Sitagliptin 100 mg0.32

Change From Baseline in Fasting Plasma Glucose at Week 12

The change from baseline is the Week 12 FPG minus the Week 0 fasting plasma glucose (LOCF). Laboratory measurements were performed after an overnight fast ≥8 hours in duration. (NCT01059825)
Timeframe: Baseline and Week 12

Interventionmg/dL (Least Squares Mean)
Placebo2.76
Ertugliflozin 1 mg-18.23
Ertugliflozin 5 mg-23.06
Ertugliflozin 10 mg-31.47
Ertugliflozin 25 mg-29.26
Sitagliptin 100 mg-17.29

Change From Baseline in Fasting Plasma Glucose at Week 2

The change from baseline is the Week 2 FPG minus the Week 0 FPG (LOCF). Laboratory measurements were performed after an overnight fast ≥8 hours in duration. (NCT01059825)
Timeframe: Baseline and Week 2

Interventionmg/dL (Least Squares Mean)
Placebo5.89
Ertugliflozin 1 mg-15.07
Ertugliflozin 5 mg-15.68
Ertugliflozin 10 mg-26.65
Ertugliflozin 25 mg-16.44
Sitagliptin 100 mg-14.69

Change From Baseline in Fasting Plasma Glucose at Week 4

The change from baseline is the Week 4 FPG minus the Week 0 FPG (LOCF). Laboratory measurements were performed after an overnight fast ≥8 hours in duration. (NCT01059825)
Timeframe: Baseline and Week 4

Interventionmg/dL (Least Squares Mean)
Placebo5.17
Ertugliflozin 1 mg-16.91
Ertugliflozin 5 mg-22.77
Ertugliflozin 10 mg-27.95
Ertugliflozin 25 mg-26.62
Sitagliptin 100 mg-18.00

Change From Baseline in Fasting Plasma Glucose at Week 8

The change from baseline is the Week 8 FPG minus the Week 0 FPG (LOCF). Laboratory measurements were performed after an overnight fast ≥8 hours in duration. (NCT01059825)
Timeframe: Baseline and Week 8

Interventionmg/dL (Least Squares Mean)
Placebo3.82
Ertugliflozin 1 mg-18.25
Ertugliflozin 5 mg-24.69
Ertugliflozin 10 mg-31.59
Ertugliflozin 25 mg-30.99
Sitagliptin 100 mg-18.93

Change From Baseline in HbA1c at Week 12

HbA1c is measured as percent. The change from baseline is the Week 12 HbA1c percent minus the Week 0 HbA1c percent (last observation carried forward [LOCF]). (NCT01059825)
Timeframe: Baseline and Week 12

InterventionPercent (Least Squares Mean)
Placebo-0.11
Ertugliflozin 1 mg-0.56
Ertugliflozin 5 mg-0.80
Ertugliflozin 10 mg-0.73
Ertugliflozin 25 mg-0.83
Sitagliptin 100 mg-0.87

Change From Baseline in HbA1C at Week 2

HbA1c is measured as percent. The change from baseline is the Week 2 HbA1c percent minus the Week 0 HbA1c percent (LOCF). (NCT01059825)
Timeframe: Baseline and Week 2

InterventionPercent (Least Squares Mean)
Placebo0.00
Ertugliflozin 1 mg-0.14
Ertugliflozin 5 mg-0.29
Ertugliflozin 10 mg-0.22
Ertugliflozin 25 mg-0.17
Sitagliptin 100 mg-0.26

Change From Baseline in HbA1c at Week 4

HbA1c is measured as percent. The change from baseline is the Week 4 HbA1c percent minus the Week 0 HbA1c percent (LOCF). (NCT01059825)
Timeframe: Baseline and Week 4

InterventionPercent (Least Squares Mean)
Placebo-0.04
Ertugliflozin 1 mg-0.40
Ertugliflozin 5 mg-0.49
Ertugliflozin 10 mg-0.48
Ertugliflozin 25 mg-0.40
Sitagliptin 100 mg-0.48

Change From Baseline in HbA1c at Week 8

HbA1c is measured as percent. The change from baseline is the Week 8 HbA1c percent minus the Week 0 HbA1c percent (LOCF). (NCT01059825)
Timeframe: Baseline and Week 8

InterventionPercent (Least Squares Mean)
Placebo-0.10
Ertugliflozin 1 mg-0.57
Ertugliflozin 5 mg-0.76
Ertugliflozin 10 mg-0.73
Ertugliflozin 25 mg-0.75
Sitagliptin 100 mg-0.77

Change From Baseline in Systolic Blood Pressure at Week 12

Sitting blood pressure was measured in triplicate and the average of the measurements taken at a single assessment time was analyzed. The change from baseline is the Week 12 systolic blood pressure minus the Week 0 systolic blood pressure (LOCF). (NCT01059825)
Timeframe: Baseline and Week 12

InterventionmmHg (Least Squares Mean)
Placebo-0.55
Ertugliflozin 1 mg-2.69
Ertugliflozin 5 mg-4.03
Ertugliflozin 10 mg-3.43
Ertugliflozin 25 mg-3.93
Sitagliptin 100 mg-1.09

Change From Baseline in Systolic Blood Pressure at Week 2

Sitting blood pressure was measured in triplicate and the average of the measurements taken at a single assessment time was analyzed. The change from baseline is the Week 2 systolic blood pressure minus the Week 0 systolic blood pressure (LOCF). (NCT01059825)
Timeframe: Baseline and Week 2

InterventionmmHg (Least Squares Mean)
Placebo-1.93
Ertugliflozin 1 mg-2.30
Ertugliflozin 5 mg-4.73
Ertugliflozin 10 mg-2.28
Ertugliflozin 25 mg-5.39
Sitagliptin 100 mg-0.91

Change From Baseline in Systolic Blood Pressure at Week 4

Sitting blood pressure was measured in triplicate and the average of the measurements taken at a single assessment time was analyzed. The change from baseline is the Week 4 systolic blood pressure minus the Week 0 systolic blood pressure (LOCF). (NCT01059825)
Timeframe: Baseline and Week 4

InterventionmmHg (Least Squares Mean)
Placebo-2.57
Ertugliflozin 1 mg-3.94
Ertugliflozin 5 mg-5.15
Ertugliflozin 10 mg-5.43
Ertugliflozin 25 mg-3.33
Sitagliptin 100 mg-3.32

Change From Baseline in Systolic Blood Pressure at Week 8

Sitting blood pressure was measured in triplicate and the average of the measurements taken at a single assessment time was analyzed. The change from baseline is the Week 8 systolic blood pressure minus the Week 0 systolic blood pressure (LOCF). (NCT01059825)
Timeframe: Baseline and Week 8

InterventionmmHg (Least Squares Mean)
Placebo-0.44
Ertugliflozin 1 mg-1.53
Ertugliflozin 5 mg-2.85
Ertugliflozin 10 mg-3.04
Ertugliflozin 25 mg-3.30
Sitagliptin 100 mg-2.43

Number of Participants Who Discontinued Study Medication Due to an AE

An adverse event is defines as any untoward medical occurrence in a clinical investigation participant administered a product or medical device; the event need not necessarily have a causal relationship with the treatment or usage. Below table includes all data collected since the first dose of sponsor-provided metformin and excludes a temporary discontinuation of study medication. (NCT01059825)
Timeframe: Up to 84 days

InterventionParticipants (Number)
Placebo1
Ertugliflozin 1 mg1
Ertugliflozin 5 mg3
Ertugliflozin 10 mg2
Ertugliflozin 25 mg1
Sitagliptin 100 mg1
Metformin Run-in3

Number of Participants Who Experienced an Advere Event (AE)

An adverse event is defines as any untoward medical occurrence in a clinical investigation participant administered a product or medical device; the event need not necessarily have a causal relationship with the treatment or usage. Below table includes all data collected since the first dose of sponsor-provided metformin. (NCT01059825)
Timeframe: Up to 98 days

InterventionParticipants (Number)
Placebo29
Ertugliflozin 1 mg31
Ertugliflozin 5 mg30
Ertugliflozin 10 mg29
Ertugliflozin 25 mg28
Sitagliptin 100 mg30
Metformin Run-in82

Percent Change From Baseline in Body Weight at Week 12

The percent change from baseline is the ([Week 12 body weight minus the Week 0 body weight] divided by the Week 0 body weight) X 100 (LOCF). (NCT01059825)
Timeframe: Baseline and Week 12

InterventionPercent change (Least Squares Mean)
Placebo-0.75
Ertugliflozin 1 mg-1.90
Ertugliflozin 5 mg-2.50
Ertugliflozin 10 mg-2.90
Ertugliflozin 25 mg-2.66
Sitagliptin 100 mg-0.30

Percent Change From Baseline in Body Weight at Week 2

The percent change from baseline is the ([Week 2 body weight minus the Week 0 body weight] divided by the Week 0 body weight) X 100 (LOCF). (NCT01059825)
Timeframe: Baseline and Week 2

InterventionPercent change (Least Squares Mean)
Placebo-0.24
Ertugliflozin 1 mg-0.65
Ertugliflozin 5 mg-1.36
Ertugliflozin 10 mg-1.14
Ertugliflozin 25 mg-1.11
Sitagliptin 100 mg0.21

Percent Change From Baseline in Body Weight at Week 4

The percent change from baseline is the ([Week 4 body weight minus the Week 0 body weight] divided by the Week 0 body weight) X 100 (LOCF). (NCT01059825)
Timeframe: Baseline and Week 4

InterventionPercent change (Least Squares Mean)
Placebo-0.44
Ertugliflozin 1 mg-1.20
Ertugliflozin 5 mg-1.76
Ertugliflozin 10 mg-1.68
Ertugliflozin 25 mg-1.52
Sitagliptin 100 mg0.01

Percent Change From Baseline in Body Weight at Week 8

The percent change from baseline is the ([Week 8 body weight minus the Week 0 body weight] divided by the Week 0 body weight) X 100 (LOCF). (NCT01059825)
Timeframe: Baseline and Week 8

InterventionPercent change (Least Squares Mean)
Placebo-0.62
Ertugliflozin 1 mg-1.65
Ertugliflozin 5 mg-2.18
Ertugliflozin 10 mg-2.30
Ertugliflozin 25 mg-2.40
Sitagliptin 100 mg-0.38

Percentage of Participants Achieving HbA1C <6.5% at Week 12

Laboratory measurements were performed after an overnight fast ≥8 hours in duration. (NCT01059825)
Timeframe: Week 12

InterventionPercentage of participants (Number)
Placebo6.7
Ertugliflozin 1 mg12.0
Ertugliflozin 5 mg20.4
Ertugliflozin 10 mg13.6
Ertugliflozin 25 mg14.9
Sitagliptin 100 mg25.5

Percentage of Participants Achieving HbA1c <7% at Week 12

Laboratory measurements were performed after an overnight fast ≥8 hours in duration. (NCT01059825)
Timeframe: Week 12

InterventionPercentage of participants (Number)
Placebo15.6
Ertugliflozin 1 mg44.0
Ertugliflozin 5 mg42.9
Ertugliflozin 10 mg38.6
Ertugliflozin 25 mg36.2
Sitagliptin 100 mg43.1

Coefficient of Variation at 26 Weeks Minus Coefficient of Variation at Baseline

The change in the coefficient of variation (CV) of continuous glucose readings, as assessed by Continuous Glucose Monitoring (CGM) (NCT01524705)
Timeframe: At baseline, 6 months of intervention

Interventionpercentage (Mean)
Insulin Glargine, Metformin, Exenatide-2.43
Insulin Glargine, Metformin, Prandial Insulin0.44

HbA1C Levels

% of glycosylated hemoglobin in whole blood at 26 weeks (NCT01524705)
Timeframe: Baseline vs 26 weeks

Intervention% of HbA1C (Mean)
Insulin Glargine, Metformin, Exenatide7.1
Insulin Glargine, Metformin, Prandial Insulin7.2

Number of Participants With Hypoglycemia

Severe hypoglycemia-documented glucose <50mg/dl (participant journal), and hypoglycemic attacks requiring hospitalization, or treatment by emergency personnel. (NCT01524705)
Timeframe: 26 weeks

InterventionParticipants (Count of Participants)
Insulin Glargine, Metformin, Exenatide0
Insulin Glargine, Metformin, Prandial Insulin0

Weight Change During Trial

Weight in kg at 26 weeks minus weight at baseline. (NCT01524705)
Timeframe: Baseline vs 26 weeks

Interventionkg (Mean)
Insulin Glargine, Metformin, Exenatide-4.8
Insulin Glargine, Metformin, Prandial Insulin0.7

Body Weight Change From Baseline

"Change from baseline in body weight after 24 weeks.~Note that adjusted means are provided." (NCT01210001)
Timeframe: Baseline and 24 weeks

Interventionkg (Mean)
Placebo0.34
Empa 10mg-1.62
Empa 25mg-1.47

Fasting Plasma Glucose (FPG) Change From Baseline

"Change from baseline in fasting plasma glucose (FPG) after 24 weeks of treatment.~Note that adjusted means are provided." (NCT01210001)
Timeframe: Baseline and 24 weeks

Interventionmg/dL (Mean)
Placebo6.47
Empa 10mg-17.00
Empa 25mg-21.99

HbA1c Change From Baseline

"Change From Baseline in HbA1c after 24 weeks.~Note that adjusted means are provided." (NCT01210001)
Timeframe: Baseline and 24 weeks

Interventionpercentage of HbA1c (Mean)
Placebo-0.11
Empa 10mg-0.59
Empa 25mg-0.72

HbA1c Change From Baseline for Pio and Met Background Medication Patients

"Change From Baseline in HbA1c after 24 weeks for patients with pioglitazone (pio) and metformin (met) background medication only.~Note that adjusted means are provided." (NCT01210001)
Timeframe: Baseline and 24 weeks

Interventionpercentage of HbA1c (Mean)
Placebo-0.11
Empa 10mg-0.55
Empa 25mg-0.70

Hypoglycaemic Events

Number of patients with hypoglycaemic events, as reported as adverse events. (NCT01210001)
Timeframe: From first drug administration until 7 days after last intake of study drug, up to 256 days

Interventionpercentage of participants (Number)
Placebo1.8
Empa 10mg1.2
Empa 25mg2.4

Change in Body Weight From Baseline to Week 26

The estimated mean change in body weight after 26 weeks of treatment. (NCT01617434)
Timeframe: Week 0 to Week 26

Interventionkg (Mean)
Liraglutide-3.54
Placebo-0.42

Change in Fasting Plasma Glucose (FPG) From Baseline to Week 26

The estimated mean change from baseline in FPG after 26 weeks of treatment. (NCT01617434)
Timeframe: Week 0 to Week 26

Interventionmmol/L (Mean)
Liraglutide-1.44
Placebo-0.16

Change in Glycosylated Haemoglobin (HbA1c) From Baseline to Week 26

The estimated mean change from baseline in HbA1c after 26 weeks of treatment. (NCT01617434)
Timeframe: Week 0 to Week 26

Interventionpercentage of glycosylated haemoglobin (Mean)
Liraglutide-1.30
Placebo-0.11

Change in Mean Self-Measured Plasma Glucose (SMPG) of 7-Point Profile From Baseline to Week 26

The estimated mean change from baseline in mean SMPG of 7-point profile (7-points were before breakfast, 90 minutes after start of breakfast, before lunch, 90 minutes after start of lunch, before dinner, 90 minutes after start of dinner and at bedtime) after 26 weeks of treatment. (NCT01617434)
Timeframe: Week 0 to Week 26

Interventionmmol/L (Mean)
Liraglutide-2.61
Placebo-1.02

Number of Minor Hypoglycaemic Episodes During The Randomised Treatment Period

A minor hypoglycaemic episode was defined as either, (a) an episode with symptoms consistent with hypoglycaemia with confirmation by blood glucose <2.8 mmol/L (50 mg/dL) or plasma glucose <3.1 mmol/L (56 mg/dL) that was handled by the subject him/herself or (b) any asymptomatic blood glucose value <2.8 mmol/L (50 mg/dL) or plasma glucose value <3.1 mmol/L (56 mg/dL). (NCT01617434)
Timeframe: Week 0 to Week 26 + 7 days follow up

InterventionEvents/100 years of patient exposure (Number)
Liraglutide126
Placebo83

Number of Severe Hypoglycaemic Episodes During The Randomised Treatment Period

Severe hypoglycaemia episode was defined as an episode requiring assistance of another person to actively administer carbohydrate, glucagon or other resuscitative actions. (NCT01617434)
Timeframe: Week 0 to Week 26 + 7 days follow up

InterventionEvents/100 years of patient exposure (Number)
Liraglutide0
Placebo0

Number of Subjects Achieving HbA1c Below 7.0% (American Diabetes Association [ADA] Target)

Number of subjects achieving HbA1c below 7.0% (American Diabetes Association [ADA] target) after 26 weeks of treatment (NCT01617434)
Timeframe: At Week 26

Interventionpercentage of subjects (Number)
Liraglutide59.24
Placebo14.02

Number of Subjects Achieving HbA1c Below or Equal to 6.5% (American Association of Clinical Endocrinologists [AACE] Target)

Number of subjects achieving HbA1c below or equal to 6.5% (American Association of Clinical Endocrinologists [AACE] target) after 26 weeks of treatment. (NCT01617434)
Timeframe: At Week 26

Interventionpercentage of subjects (Number)
Liraglutide42.91
Placebo3.60

Number of Adverse Events (AEs) During The Randomised Treatment Period

An AE was defined as treatment emergent if the onset date (or increase in severity) was on or after the first day of exposure to randomised treatment and no later than 7 days after the last day of randomised treatment. The adverse events were categorised as 'serious' and 'non-serious' adverse events. Adverse events were also categorised according to the severity as 'mild', 'moderate' and 'severe' adverse events. (NCT01617434)
Timeframe: Week 0 to Week 26 + 7 days follow up

,
InterventionEvents/1000 years of patient exposure (Number)
Adverse EventsSerious Adverse EventsSevere Adverse EventsModerate Adverse EventsMild Adverse Events
Liraglutide491814916912743474
Placebo373710110110602575

Apgar Score at 5 Min After Delivery Per Arm

Apgar score 0-10. 0-2 points from heart rate; 0-2 points for respiratory effort; 0-2 points for skin colour; 0-2 points for muscle tone; 0-2 points for reflex response. For all items the higher the value, the better the outcome (NCT01240785)
Timeframe: 5 minutes after delivery

Interventionunits on a scale (Mean)
Metformin8.7
Insulin8.9

Birth Weight Per Arm

birth weight adjusted for gestational weeks expressed as standard deviation units using data from Finnish fetal growth charts in normal pregnancies (NCT01240785)
Timeframe: delivery

Interventiong (Mean)
Metformin3604
Insulin3589

Gestational Weeks at Delivery Per Arm

(NCT01240785)
Timeframe: delivery

Interventionweeks (Mean)
Metformin39.2
Insulin39.3

Induction of Delivery Per Arm

(NCT01240785)
Timeframe: delivery

Interventionparticipants (Number)
Metformin42
Insulin58

Maternal Weight Gain Per Arm

(NCT01240785)
Timeframe: up to on the average 40 weeks of gestation

Interventionkg (Mean)
Metformin8.0
Insulin7.9

Mode of Delivery Per Arm

(NCT01240785)
Timeframe: delivery

Interventionno of cesarean section (Number)
Metformin15
Insulin18

Neonatal Hyperbilirubinemia Per Arm

(NCT01240785)
Timeframe: 0-3 days after delivery

Interventionparticipants (Number)
Metformin9
Insulin10

Neonatal Hypoglycemia Per Arm

(NCT01240785)
Timeframe: 0-24 h after delivery

Interventionparticipants (Number)
Metformin18
Insulin18

Neonate Transfer to Intensive Care Unit Per Arm

(NCT01240785)
Timeframe: 0-5 days after delivery

Interventionparticipants (Number)
Metformin34
Insulin39

Pre-eclampsia Per Arm

(NCT01240785)
Timeframe: up to on the average 40 weeks of gestation

Interventionparticipants (Number)
Metformin5
Insulin10

Pregnancy Induced Hypertension Per Arm

Participants with pregnancy induced hypertension defined as blood pressure over 140/90 mmHg or increase in systolic blood pressure > 30 mmHg or diastolic blood pressure > 15 mmHg (NCT01240785)
Timeframe: up to on the average 40 weeks of gestation

Interventionparticipants (Number)
Metformin2
Insulin4

Shoulder Dystocia Per Arm

(NCT01240785)
Timeframe: delivery

Interventionparticipants (Number)
Metformin1
Insulin2

Change in Fasting Plasma Glucose (FPG) From Baseline to Week 52

The table below shows the least-squares (LS) mean change in FPG from Baseline to Week 52 for each treatment group. The statistical analysis shows the treatment difference (ie, between canagliflozin and sitagliptin) in the LS mean change. (NCT01137812)
Timeframe: Day 1 (Baseline) and Week 52

Interventionmg/dL (Least Squares Mean)
Canagliflozin 300 mg-29.9
Sitagliptin 100 mg-5.85

Change in HbA1c From Baseline to Week 52

The table below shows the least-squares (LS) mean change in HbA1c from Baseline to Week 52 for each treatment group. The statistical analysis shows the treatment difference (ie, between canagliflozin and sitagliptin) in the LS mean change. (NCT01137812)
Timeframe: Day 1 (Baseline) and Week 52

InterventionPercent (Least Squares Mean)
Canagliflozin 300 mg-1.03
Sitagliptin 100 mg-0.66

Change in Systolic Blood Pressure (SBP) From Baseline to Week 52

The table below shows the least-squares (LS) mean change in SBP from Baseline to Week 52 for each treatment group. The statistical analysis shows the treatment difference (ie, between canagliflozin and sitagliptin) in the LS mean change. (NCT01137812)
Timeframe: Day 1 (Baseline) and Week 52

InterventionmmHg (Least Squares Mean)
Canagliflozin 300 mg-5.06
Sitagliptin 100 mg0.85

Percent Change in Body Weight From Baseline to Week 52

The table below shows the least-squares (LS) mean percent change in body weight from Baseline to Week 52 for each treatment group. The statistical analysis shows the treatment difference (ie, between canagliflozin and sitagliptin) in the LS mean percent change. (NCT01137812)
Timeframe: Day 1 (Baseline) and Week 52

InterventionPercent change (Least Squares Mean)
Canagliflozin 300 mg-2.5
Sitagliptin 100 mg0.3

Percent Change in High-density Lipoprotein Cholesterol (HDL-C) From Baseline to Week 52

The table below shows the mean percent change in HDL-C from Baseline to Week 52 for each treatment group. The statistical analysis shows the treatment difference (ie, between canagliflozin and sitagliptin) in the LS mean change. (NCT01137812)
Timeframe: Day 1 (Baseline) and Week 52

InterventionPercent change (Least Squares Mean)
Canagliflozin 300 mg7.6
Sitagliptin 100 mg0.6

Percent Change in Triglycerides From Baseline to Week 52

The table below shows the mean percent change in triglycerides from Baseline to Week 52 for each treatment group. The statistical analysis shows the treatment difference (ie, between canagliflozin and sitagliptin) in the LS mean change. (NCT01137812)
Timeframe: Day 1 (Baseline) and Week 52

InterventionPercent change (Least Squares Mean)
Canagliflozin 300 mg9.6
Sitagliptin 100 mg11.9

Percentage of Patients With HbA1c <7% at Week 52

The table below shows the percentage of patients with HbA1c <7% at Week 52 in each treatment group. The statistical analysis shows the treatment difference (ie, between canagliflozin and sitagliptin) in the percentage. (NCT01137812)
Timeframe: Week 52

InterventionPercentage of patients (Number)
Canagliflozin 300 mg47.6
Sitagliptin 100 mg35.3

Change in 2-hour Post-prandial Glucose From Baseline to Week 26 (High Glycemic Substudy)

The table below shows the least-squares (LS) mean change in 2-hour post-prandial glucose from Baseline to Week 26 for each treatment group in patients randomized to the High Glycemic Substudy. (NCT01081834)
Timeframe: Day 1 (Baseline) and Week 26

Interventionmg/dL (Least Squares Mean)
Canagliflozin 100 mg-118
Canagliflozin 300 mg-126

Change in 2-hour Post-prandial Glucose From Baseline to Week 26 (Main Study)

The table below shows the least-squares (LS) mean change in 2-hour post-prandial glucose from Baseline to Week 26 for each treatment group. The statistical analyses show the treatment differences (ie, each canagliflozin group minus placebo) in the LS mean change. (NCT01081834)
Timeframe: Day 1 (Baseline) and Week 26

Interventionmg/dL (Least Squares Mean)
Placebo5.19
Canagliflozin 100 mg-42.9
Canagliflozin 300 mg-58.8

Change in Fasting Plasma Glucose (FPG) From Baseline to Week 26 (High Glycemic Substudy)

The table below shows the least-squares (LS) mean change in FPG from Baseline to Week 26 for each treatment group in patients randomized to the High Glycemic Substudy. (NCT01081834)
Timeframe: Day 1 (Baseline) and Week 26

Interventionmg/dL (Least Squares Mean)
Canagliflozin 100 mg-81.7
Canagliflozin 300 mg-86.3

Change in Fasting Plasma Glucose (FPG) From Baseline to Week 26 (Main Study)

The table below shows the least-squares (LS) mean change in FPG from Baseline to Week 26 for each treatment group. The statistical analyses show the treatment differences (ie, each canagliflozin group minus placebo) in the LS mean change. (NCT01081834)
Timeframe: Day 1 (Baseline) and Week 26

Interventionmg/dL (Least Squares Mean)
Placebo8.33
Canagliflozin 100 mg-27.2
Canagliflozin 300 mg-35.0

Change in HbA1c From Baseline to Week 26 (High Glycemic Substudy)

The table below shows the least-squares (LS) mean change in HbA1c from Baseline to Week 26 for each treatment group in patients randomized to the High Glycemic Substudy. (NCT01081834)
Timeframe: Day 1 (Baseline) and Week 26

InterventionPercent (Least Squares Mean)
Canagliflozin 100 mg-2.13
Canagliflozin 300 mg-2.56

Change in HbA1c From Baseline to Week 26 (Main Study)

The table below shows the least-squares (LS) mean change in HbA1c from Baseline to Week 26 for each treatment group. The statistical analyses show the treatment differences (ie, each canagliflozin group minus placebo) in the LS mean change. (NCT01081834)
Timeframe: Day 1 (Baseline) and Week 26

InterventionPercent (Least Squares Mean)
Placebo0.14
Canagliflozin 100 mg-0.77
Canagliflozin 300 mg-1.03

Change in Systolic Blood Pressure (SBP) From Baseline to Week 26 (High Glycemic Substudy)

The table below shows the least-squares (LS) mean change in SBP from Baseline to Week 26 for each treatment group in patients randomized to the High Glycemic Substudy. (NCT01081834)
Timeframe: Day 1 (Baseline) and Week 26

InterventionmmHg (Least Squares Mean)
Canagliflozin 100 mg-4.47
Canagliflozin 300 mg-4.97

Change in Systolic Blood Pressure (SBP) From Baseline to Week 26 (Main Study)

The table below shows the least-squares (LS) mean change in SBP from Baseline to Week 26 for each treatment group. The statistical analyses show the treatment differences (ie, each canagliflozin group minus placebo) in the LS mean change. (NCT01081834)
Timeframe: Day 1 (Baseline) and Week 26

InterventionmmHg (Least Squares Mean)
Placebo0.38
Canagliflozin 100 mg-3.34
Canagliflozin 300 mg-5.04

Percent Change in Body Weight From Baseline to Week 26 (High Glycemic Substudy)

The table below shows the least-squares (LS) mean percent change in body weight from Baseline to Week 26 for each treatment group in patients randomized to the High Glycemic Substudy. (NCT01081834)
Timeframe: Day 1 (Baseline) and Week 26

InterventionPercent change (Least Squares Mean)
Canagliflozin 100 mg-3.0
Canagliflozin 300 mg-3.8

Percent Change in Body Weight From Baseline to Week 26 (Main Study)

The table below shows the least-squares (LS) mean percent change in body weight from Baseline to Week 26 for each treatment group. The statistical analyses show the treatment differences (ie, each canagliflozin group minus placebo) in the LS mean percent change. (NCT01081834)
Timeframe: Day 1 (Baseline) and Week 26

InterventionPercent change (Least Squares Mean)
Placebo-0.6
Canagliflozin 100 mg-2.8
Canagliflozin 300 mg-3.9

Percent Change in High-density Lipoprotein Cholesterol (HDL-C) From Baseline to Week 26 (High Glycemic Substudy)

The table below shows the least-squares mean percent change in HDL-C from Baseline to Week 26 for each treatment group in patients randomized to the High Glycemic Substudy. (NCT01081834)
Timeframe: Day 1 (Baseline) and Week 26

InterventionPercent change (Least Squares Mean)
Canagliflozin 100 mg2.4
Canagliflozin 300 mg10.8

Percent Change in High-density Lipoprotein Cholesterol (HDL-C) From Baseline to Week 26 (Main Study)

The table below shows the least-squares (LS) mean percent change in HDL-C from Baseline to Week 26 for each treatment group. The statistical analyses show the treatment differences (ie, each canagliflozin group minus placebo) in the LS mean percent change. (NCT01081834)
Timeframe: Day 1 (Baseline) and Week 26

InterventionPercent change (Least Squares Mean)
Placebo4.4
Canagliflozin 100 mg11.2
Canagliflozin 300 mg10.5

Percent Change in Triglycerides From Baseline to Week 26 (High Glycemic Substudy)

The table below shows the least-squares mean percent change in triglycerides from Baseline to Week 26 for each treatment group in patients randomized to the High Glycemic Substudy. (NCT01081834)
Timeframe: Day 1 (Baseline) and Week 26

InterventionPercent change (Least Squares Mean)
Canagliflozin 100 mg-0.6
Canagliflozin 300 mg-12.7

Percent Change in Triglycerides From Baseline to Week 26 (Main Study)

The table below shows the least-squares (LS) mean percent change in triglycerides from Baseline to Week 26 for each treatment group. The statistical analyses show the treatment differences (ie, each canagliflozin group minus placebo) in the LS mean percent change. (NCT01081834)
Timeframe: Day 1 (Baseline) and Week 26

InterventionPercent change (Least Squares Mean)
Placebo7.8
Canagliflozin 100 mg2.5
Canagliflozin 300 mg-2.4

Percentage of Patients With HbA1c <7% at Week 26 (High Glycemic Substudy)

The table below shows the percentage of patients with HbA1c <7% at Week 26 for each treatment group in patients randomized to the High Glycemic Substudy. (NCT01081834)
Timeframe: Week 26

InterventionPercentage of patients (Number)
Canagliflozin 100 mg17.4
Canagliflozin 300 mg11.6

Percentage of Patients With HbA1c <7% at Week 26 (Main Study)

The table below shows the percentage of patients with HbA1c <7% at Week 26. The statistical analyses show the treatment differences (ie, each canagliflozin group minus placebo) in the percentage. (NCT01081834)
Timeframe: Week 26

InterventionPercentage of patients (Number)
Placebo20.6
Canagliflozin 100 mg44.5
Canagliflozin 300 mg62.4

Change in Fasting Plasma Glucose (FPG) From Baseline to Week 26

The table below shows the least-squares (LS) mean change in FPG from Baseline to Week 26 for each treatment group. The statistical analyses show the treatment differences (ie, each canagliflozin group minus placebo) in the LS mean change. (NCT01106625)
Timeframe: Day 1 (Baseline) and Week 26

Interventionmg/dL (Least Squares Mean)
Placebo4.11
Canagliflozin 100 mg-18.2
Canagliflozin 300 mg-30.5

Change in HbA1c From Baseline to Week 26

The table below shows the least-squares (LS) mean change in HbA1c from Baseline to Week 26 for each treatment group. The statistical analyses show the treatment differences (ie, each canagliflozin group minus placebo) in the LS mean change. (NCT01106625)
Timeframe: Day 1 (Baseline) and Week 26

InterventionPercent (Least Squares Mean)
Placebo-0.13
Canagliflozin 100 mg-0.85
Canagliflozin 300 mg-1.06

Change in Systolic Blood Pressure (SBP) From Baseline to Week 26

The table below shows the least-squares (LS) mean change in SBP from Baseline to Week 26 for each treatment group. The statistical analyses show the treatment differences (ie, each canagliflozin group minus placebo) in the LS mean change. (NCT01106625)
Timeframe: Day 1 (Baseline) and Week 26

InterventionmmHg (Least Squares Mean)
Placebo-2.65
Canagliflozin 100 mg-4.89
Canagliflozin 300 mg-4.27

Percent Change in Body Weight From Baseline to Week 26

The table below shows the least-squares (LS) mean percent change in body weight from Baseline to Week 26 for each treatment group. The statistical analyses show the treatment differences (ie, each canagliflozin group minus placebo) in the LS mean percent change. (NCT01106625)
Timeframe: Day 1 (Baseline) and Week 26

InterventionPercent change (Least Squares Mean)
Placebo-0.7
Canagliflozin 100 mg-2.1
Canagliflozin 300 mg-2.6

Percent Change in High-density Lipoprotein Cholesterol (HDL-C) From Baseline to Week 26

The table below shows the least-squares (LS) mean percent change in HDL-C from Baseline to Week 26 for each treatment group. The statistical analyses show the treatment differences (ie, each canagliflozin group minus placebo) in the LS mean percent change. (NCT01106625)
Timeframe: Day 1 (Baseline) and Week 26

InterventionPercent change (Least Squares Mean)
Placebo3.2
Canagliflozin 100 mg5.7
Canagliflozin 300 mg6.5

Percent Change in Triglycerides From Baseline to Week 26

The table below shows the least-squares (LS) mean percent change in triglycerides from Baseline to Week 26 for each treatment group. The statistical analyses show the treatment differences (ie, each canagliflozin group minus placebo) in the LS mean percent change. (NCT01106625)
Timeframe: Day 1 (Baseline) and Week 26

InterventionPercent change (Least Squares Mean)
Placebo11.6
Canagliflozin 100 mg5.4
Canagliflozin 300 mg8.5

Percentage of Patients With HbA1c <7% at Week 26

The table below shows the percentage of patients with HbA1c<7% at Week 26 in each treatment group. The statistical analyses show the treatment differences (ie, each canagliflozin group minus placebo) in the percentage. (NCT01106625)
Timeframe: Week 26

InterventionPercentage of patients (Number)
Placebo18
Canagliflozin 100 mg43.2
Canagliflozin 300 mg56.6

Change in Body Composition

Change in percent body fat (NCT01881828)
Timeframe: 0-26 weeks

Interventionpercentage of change (Mean)
Metformin-0
Oral Placebo1

Change in Body Mass Index (BMI)

(NCT01881828)
Timeframe: 0-26 weeks

Interventionpercentile (Mean)
Metformin-1
Oral Placebo1

Change in Total Daily Dose of Insulin (TDI) Per kg

(NCT01881828)
Timeframe: 0-26 weeks

Interventioninsulin per kg (Mean)
Metformin-0.1
Oral Placebo-0.0

Change in Waist Circumference

(NCT01881828)
Timeframe: 0-26 weeks

Interventioncentimeters (Mean)
Metformin-0
Oral Placebo1

Change in Blood Pressure

(NCT01881828)
Timeframe: 0-26 weeks

,
Interventionmm Hg (Mean)
Change in SystolicChange in Diastolic
Metformin00
Oral Placebo-00

Change in Hemoglobin A1c From Baseline to 26 Weeks, Adjusted for Baseline Hemoglobin A1c.

Hemoglobin A1c is a measure of glycemic control over approximately the past 3 months (NCT01881828)
Timeframe: 0-26 weeks

,
Interventionpercentage (Mean)
HbA1cChange from Baseline to 26 Weeks
Metformin9.00.2
Oral Placebo8.90.2

Change in Hemoglobin A1c From Baseline to 26 Weeks, Adjusted for Baseline Hemoglobin A1c.

Hemoglobin A1c is a measure of glycemic control over approximately the past 3 months (NCT01881828)
Timeframe: 0-26 weeks

,
Interventionpercentage of participants (Number)
HbA1c Decrease ≥0.5%HbA1c Increase ≥0.5%HbA1c <7.5%
Metformin19443
Oral Placebo18354

Change in Serum Lipids

(NCT01881828)
Timeframe: 0-26 weeks

,
Interventionmg/dL (Mean)
Change in LDLChange in VLDLChange in HDLChange in TriglyceridesChange in Total Cholesterol
Metformin-6-0-04-5
Oral Placebo21-163

Change in Fasting Plasma Glucose (FPG) From Baseline to Week 26

The table below shows the least-squares (LS) mean change in FPG from Baseline to Week 26 for each treatment group. The statistical analyses show the treatment differences (ie, each canagliflozin group minus placebo) in the LS mean change. (NCT01106651)
Timeframe: Day 1 (Baseline) and Week 26

Interventionmg/dL (Least Squares Mean)
Placebo7.39
Canagliflozin 100 mg-18.1
Canagliflozin 300 mg-20.3

Change in HbA1c From Baseline to Week 26

The table below shows the least-squares (LS) mean change in HbA1c from Baseline to Week 26 for each treatment group. The statistical analyses show the treatment differences (ie, each canagliflozin group minus placebo) in the LS mean change. (NCT01106651)
Timeframe: Day 1 (Baseline) and Week 26

InterventionPercent (Least Squares Mean)
Placebo-0.03
Canagliflozin 100 mg-0.60
Canagliflozin 300 mg-0.73

Change in Region Percent Total Fat From Baseline to Week 26 in a Subset of Patients Undergoing Specific Dual-energy X-ray Absorptiometry (DXA) Analysis for Body Composition

Region percent total fat = body fat as a percentage of (body fat + lean body mass + bone mass content). The table below shows the least-squares (LS) mean change in region percent total fat from Baseline to Week 26 for each treatment group in patients randomized to the subset of patients undergoing specific dual-energy X-ray absorptiometry (DXA) analysis for body composition. The statistical analyses show the treatment differences (ie, each canagliflozin group minus placebo) in the LS mean change. (NCT01106651)
Timeframe: Day 1 (Baseline) and Week 26

InterventionPercent (Least Squares Mean)
Placebo0.00
Canagliflozin 100 mg-1.03
Canagliflozin 300 mg-1.18

Change in Systolic Blood Pressure (SBP) From Baseline to Week 26

The table below shows the least-squares (LS) mean change in SBP from Baseline to Week 26 for each treatment group. The statistical analyses show the treatment differences (ie, each canagliflozin group minus placebo) in the LS mean change. (NCT01106651)
Timeframe: Day 1 (Baseline) and Week 26

InterventionmmHg (Least Squares Mean)
Placebo1.10
Canagliflozin 100 mg-3.52
Canagliflozin 300 mg-6.79

Change in Tissue Percent Total Fat From Baseline to Week 26 in a Subset of Patients Undergoing Specific Dual-energy X-ray Absorptiometry (DXA) Analysis for Body Composition

Tissue percent total fat = body fat as a percentage of body fat + lean body mass. The table below shows the least-squares (LS) mean change in tissue percent total fat from Baseline to Week 26 for each treatment group in patients randomized to the subset of patients undergoing specific DXA analysis for body composition. The statistical analyses show the treatment differences (ie, each canagliflozin group minus placebo) in the LS mean change. (NCT01106651)
Timeframe: Day 1 (Baseline) and Week 26

InterventionPercent (Least Squares Mean)
Placebo0.02
Canagliflozin 100 mg-1.04
Canagliflozin 300 mg-1.18

Change in Total Fat From Baseline to Week 26 in a Subset of Patients Undergoing Specific Dual-energy X-ray Absorptiometry (DXA) Analysis for Body Composition

The table below shows the least-squares (LS) mean change in total fat from Baseline to Week 26 for each treatment group in patients randomized to the subset of patients undergoing specific DXA analysis for body composition. The statistical analyses show the treatment differences (ie, each canagliflozin group minus placebo) in the LS mean change. (NCT01106651)
Timeframe: Day 1 (Baseline) and Week 26

Interventionkg (Least Squares Mean)
Placebo-0.28
Canagliflozin 100 mg-1.87
Canagliflozin 300 mg-2.38

Percent Change in Body Weight From Baseline to Week 26

The table below shows the least-squares (LS) mean percent change in body weight from Baseline to Week 26 for each treatment group. The statistical analyses show the treatment differences (ie, each canagliflozin group minus placebo) in the LS mean change. (NCT01106651)
Timeframe: Day 1 (Baseline) and Week 26

InterventionPercent change (Least Squares Mean)
Placebo-0.1
Canagliflozin 100 mg-2.4
Canagliflozin 300 mg-3.1

Percent Change in Distal Forearm Bone Mineral Density (BMD) From Baseline to Week 26

The table below shows the least-squares (LS) mean percent change from Baseline to Week 26 in distal forearm BMD for each treatment group as assessed by dual-energy X-ray absorptiometry (DXA). The statistical analyses show the treatment differences (ie, each canagliflozin group minus placebo) in LS mean percent change. (NCT01106651)
Timeframe: Day 1 (Baseline) and Week 26

InterventionPercent change (Least Squares Mean)
Placebo-0.5
Canagliflozin 100 mg-0.7
Canagliflozin 300 mg-0.8

Percent Change in Femoral Neck Bone Mineral Density (BMD) From Baseline to Week 26

The table below shows the least-squares (LS) mean percent change from Baseline to Week 26 in femoral neck BMD for each treatment group as assessed by dual-energy X-ray absorptiometry (DXA). The statistical analyses show the treatment differences (ie, each canagliflozin group minus placebo) in LS mean percent change. (NCT01106651)
Timeframe: Day 1 (Baseline) and Week 26

InterventionPercent change (Least Squares Mean)
Placebo-1.0
Canagliflozin 100 mg-0.7
Canagliflozin 300 mg-0.6

Percent Change in High-density Lipoprotein Cholesterol (HDL-C) From Baseline to Week 26

The table below shows the least-squares (LS) mean percent change in HDL-C from Baseline to Week 26 or each treatment group. The statistical analyses show the treatment differences (ie, each canagliflozin group minus placebo) in the LS mean change. (NCT01106651)
Timeframe: Day 1 (Baseline) and Week 26

InterventionPercent change (Least Squares Mean)
Placebo1.5
Canagliflozin 100 mg6.8
Canagliflozin 300 mg6.2

Percent Change in Lumbar Spine Bone Mineral Density (BMD) From Baseline to Week 26

The table below shows the least-squares (LS) mean percent change from Baseline to Week 26 in lumbar spine BMD for each treatment group as assessed by dual-energy X-ray absorptiometry (DXA). The statistical analyses show the treatment differences (ie, each canagliflozin group minus placebo) in LS mean percent change. (NCT01106651)
Timeframe: Day 1 (Baseline) and Week 26

InterventionPercent change (Least Squares Mean)
Placebo0.5
Canagliflozin 100 mg0.7
Canagliflozin 300 mg0.2

Percent Change in Total Hip Bone Mineral Density (BMD) From Baseline to Week 26

The table below shows the least-squares (LS) mean percent change from Baseline to Week 26 in total hip BMD for each treatment group as assessed by dual-energy X-ray absorptiometry (DXA). The statistical analyses show the treatment differences (ie, each canagliflozin group minus placebo) in LS mean percent change. (NCT01106651)
Timeframe: Day 1 (Baseline) and Week 26

InterventionPercent change (Least Squares Mean)
Placebo-0.5
Canagliflozin 100 mg-0.9
Canagliflozin 300 mg-1.0

Percent Change in Triglycerides From Baseline to Week 26

The table below shows the least-squares (LS) mean percent change in triglycerides from Baseline to Week 26 for each treatment group. The statistical analyses show the treatment differences (ie, each canagliflozin group minus placebo) in the LS mean change. (NCT01106651)
Timeframe: Day 1 (Baseline) and Week 26

InterventionPercent change (Least Squares Mean)
Placebo7.7
Canagliflozin 100 mg2.8
Canagliflozin 300 mg8.4

Percentage of Patients With HbA1c <7% at Week 26

The table below shows the percentage of patients with HbA1c <7% at Week 26 in each treatment group. The statistical analyses show the treatment differences (ie, each canagliflozin group minus placebo) in the percentage. (NCT01106651)
Timeframe: Week 26

InterventionPercentage of patients (Number)
Placebo28.0
Canagliflozin 100 mg47.7
Canagliflozin 300 mg58.5

Change From Baseline in 7-point Self-measured Plasma Glucose Profile

Mean change from baseline in mean of 7-point self-measured plasma glucose at week 26. The 7-point self-measured plasma glucose levels were measured before and after (120 minutes after the start of the meal) the three main meals (breakfast, lunch and dinner), and at bed time. (NCT02008682)
Timeframe: Week 0, week 26

Interventionmmol/L (Mean)
Liraglutide-2.25
Sitagliptin-1.36

Change From Baseline in Fasting Plasma Glucose

Mean change from baseline in fasting plasma glucose (FPG) at Week 26. (NCT02008682)
Timeframe: Week 0, week 26

Interventionmmol/L (Mean)
Liraglutide-2.347
Sitagliptin-1.205

Change From Baseline in Glycosylated Haemoglobin (HbA1c)

Mean change from baseline in glycosylated haemoglobin A1c (HbA1c) at Week 26. (NCT02008682)
Timeframe: Week 0, week 26

InterventionPercent (%) glycosylated haemoglobin (Mean)
Liraglutide-1.666
Sitagliptin-0.969

Number of Confirmed Hypoglycaemic Episodes

confirmed hypoglycaemic episode defined as severe (unable to treat her/himself) or biochemically confirmed by a plasma glucose < 3.1 mmol/L (NCT02008682)
Timeframe: Weeks 0-26

Interventionepisodes (Number)
Liraglutide2
Sitagliptin1

Subjects Who Achieve (Yes/no) HbA1c Below 7.0 % (American Diabetes Association Target)

Calculated as the percentage of subjects achieving treatment target of HbA1c < 7.0% at Week 26 (NCT02008682)
Timeframe: After 26 weeks of treatment

Interventionpercentage of subjects (Number)
Liraglutide76.5
Sitagliptin52.6

Subjects Who Achieve (Yes/no) HbA1c Below or Equal to 6.5 % (American Association of Clinical Endocrinologists Target)

Calculated as the percentage of subjects achieving treatment target of HbA1c <= 6.5% at Week 26 (NCT02008682)
Timeframe: After 26 weeks of treatment

Interventionpercentage of subjects (Number)
Liraglutide61.7
Sitagliptin26.3

Change From Baseline in Clinical Chemistry Parameter of Triiodothyronine (T3) Uptake During the Double-blind Treatment Period of Part B and C

The assessments were done pre-dose at Day -1 and Day 42. Baseline value was defined as the assessment done Day -1. Change from Baseline was calculated by subtracting the Baseline value from the individual post-Baseline (Day 42) value. If either the Baseline or post-Baseline value was missing, the change from Baseline was set to be missing. (NCT01725126)
Timeframe: Baseline (Day -1) and Day 42

InterventionRatio (Mean)
Part B-Placebo+Liraglutide-0.018
Part B-GSK2890457+Liraglutide-0.009
Part C-Placebo+Metformin0.002
Part C-GSK2890457+Metformin-0.001

Change From Baseline in Fasting Glucose During the Double-blind Treatment Period of Part B and C

Baseline was defined as the assessment done on Day -1. Change from Baseline was calculated by subtracting the Baseline (Day -1) values from the post-Baseline value (Day 42). Adjusted mean is reported as LS mean. (NCT01725126)
Timeframe: Baseline (Day -1) and Day 42 of Part B and C

Interventionmmol/L (Least Squares Mean)
Part B-Placebo+Liraglutide-0.384
Part B-GSK2890457+Liraglutide-0.230
Part C-Placebo+Metformin0.136
Part C-GSK2890457+Metformin-0.387

Change From Baseline in Glycated Hemoglobin (HbA1c) During the Double-blind Treatment Period of Part B and C

Baseline was defined as the assessment done on Day -1. Change from Baseline was calculated by subtracting the Baseline (Day -1) values from the post-Baseline value (Day 42). Adjusted mean is reported as LS mean. (NCT01725126)
Timeframe: Baseline (Day -1) and Day 42

InterventionPercent of TL hemoglobin (Least Squares Mean)
Part B-Placebo+Liraglutide-0.214
Part B-GSK2890457+Liraglutide-0.278
Part C-Placebo+Metformin0.018
Part C-GSK2890457+Metformin-0.201

Change From Baseline in Homeostasis Model of Assessment-Insulin Resistance (HOMA-IR]) During the Double-blind Treatment Period of Part B and C

HOMA-IR was calculated from the Day -1 and Day 42 fasting glucose and insulin values using dataset generated from the HOMA-2 model. It contained the estimates for HOMA-% insulin sensitivity (S) for pairs of fasting glucose and fasting insulin values. Study data was merged with the HOMA dataset by glucose and insulin. HOMA-IR was calculated as 100/HOMA-%S. HOMA-IR was not determined for any values outside the ranges of plasma glucose 3.5 to 25.0 mmol/L (63 - 450 mg/dL) and plasma insulin 20 to 400 pmol/L. Baseline was defined as the assessment done on Day -1. Change from Baseline was calculated by subtracting the Baseline (Day -1) values from the post-Baseline value (Day 42). Data for Part C of the study was not collected because fasting glucose and insulin were not available at the specified time points. (NCT01725126)
Timeframe: Baseline (Day -1) and Day 42

InterventionmU*mmol/L^2 (Mean)
Part B-Placebo+Liraglutide-0.150
Part B-GSK2890457+Liraglutide0.017

Change From Baseline in Matsuda Index During the Double Blind-treatment Period of Part B and C

The matsuda index was calculated from the Day -1 and Day 42 glucose and insulin results as 10,000 divided by (fasting plasma glucose x fasting plasma insulin x mean glucose at 0-2 hour post-dose x mean insulin at 0-2 hour post dose)^1/2, where glucose was measured in mmol/L and insulin in pmol/L. Baseline was defined as the assessment done on Day -1. Change from Baseline was calculated by subtracting the Baseline (Day -1) values from the post-Baseline value (Day 42). Data for Part C of the study was not collected because fasting glucose and insulin were not available at the specified time points. (NCT01725126)
Timeframe: Baseline (Day -1) and Day 42

InterventionDeciliter*mL/mg*mU (Mean)
Part B-Placebo+Liraglutide-0.991
Part B-GSK2890457+Liraglutide-0.602

Number of Participants With Any Hypoglycemic Events During Part A

Hypoglycemia is defined as symptoms consistent with hypoglycemia (e.g. dizziness, light-headedness, shakiness) which are confirmed by glucometer measurement of complete blood count (CBG) or plasma glucose value of <50 milligram per deciliter (mg/dL) for Part A or <70 mg/dL for Parts B and C (when possible, CBG values were confirmed with a laboratory measurement). In situations when no glucose sample could be measured at the time of the event, the investigator, at his or her discretion, characterized an event as 'hypoglycemia' based on reported signs and symptoms alone. Healthy participant also had asymptomatic blood glucose values <70 mg/dL as a physiological response to altered food intake (e.g., fasting). (NCT01725126)
Timeframe: Up to Follow-up (8 weeks)

InterventionParticipants (Count of Participants)
Part A-Placebo0
Part A-GSK28904570

Number of Participants With Any Hypoglycemic Events During Part B and Part C

Hypoglycemia is defined as symptoms consistent with hypoglycemia (e.g. dizziness, light-headedness, shakiness) which are confirmed by glucometer measurement of CBG or plasma glucose value of <50 mg/dL for Part A or <70 mg/dL for Parts B and C (when possible, CBG values were confirmed with a laboratory measurement). In situations when no glucose sample could be measured at the time of the event, the investigator, at his or her discretion, characterized an event as 'hypoglycemia' based on reported signs and symptoms alone. Healthy participant also had asymptomatic blood glucose values <70 mg/dL as a physiological response to altered food intake (e.g., fasting). (NCT01725126)
Timeframe: Up to Follow-up (8 weeks)

InterventionParticipants (Count of Participants)
Part B-Placebo+Liraglutide0
Part B-GSK2890457+Liraglutide0
Part C-Placebo+Metformin0
Part C-GSK2890457+Metformin0

Area Under Plasma Concentration From Time Zero (Pre-dose) to Last Time of Quantifiable Concentration (AUC [0-t]) of Liraglutide During the Double-blind Treatment Period of Part B

Blood samples were collected on Day -1 and 42 at pre-dose (0 hour), 15 minutes, 30 minutes, 1, 1.5, 2, 4 (pre-lunch), 5.5, 6, 8, 10 (pre-dinner), 11.5, 12, 14 and 24 hours post dose. The AUC (0-t) was determined using the linear trapezoidal rule for increasing concentrations and the logarithmic trapezoidal rule for decreasing concentrations. The analysis population included Liraglutide Pharmacokinetic (PK) Population in Part B comprising of all participants in All Subjects Population for whom a PK sample was obtained and analyzed for Liraglutide. (NCT01725126)
Timeframe: Day -1 and 42 at pre-dose (0 hour), 15 minutes, 30 minutes, 1, 1.5, 2, 4, 5.5, 6, 8, 10, 11.5, 12, 14 and 24 hours post-dose

,
InterventionHour*nanograms/mL (Geometric Mean)
Day -1Day 42
Part B-GSK2890457+Liraglutide1268.651265.92
Part B-Placebo+Liraglutide2210.152505.23

AUC of Metformin From Time 0 to 10 Hours Post-dose (AUC [0-10 Hour]) During the Double-blind Treatment Period of Part A

Blood samples were collected on Day 1 and 42 at pre-dose (0 hour), 15 minutes, 30 minutes, 1, 1.5, 2, 4 (pre-lunch), 5.5, 6, 8 and 10 (pre-dinner) hours post-dose. The AUC (0-10 hour) was determined using the linear trapezoidal rule for increasing concentrations and the logarithmic trapezoidal rule for decreasing concentrations. The analysis population included Metformin PK Population in Part A comprising of all participants in All Subjects Population for whom a PK sample was obtained and analyzed for metformin. (NCT01725126)
Timeframe: Day 1 and Day 42 at pre-dose (0 hour), 15 minutes, 30 minutes, 1, 1.5, 2, 4, 5.5, 6, 8 and 10 hours post-dose

,
InterventionHour*nanograms/mL (Geometric Mean)
Day 1Day 42
Part A-GSK28904573402.62231.7
Part A-Placebo4346.85081.9

Change From Baseline in Clinical Chemistry Parameters of Albumin and Total Protein During the Double-blind Treatment Period of Part A

The assessments were done pre-dose at Day 1, Day 7, Day 14, Day 28 and Day 42. Baseline value was defined as the assessment done on Day 1. Change from Baseline was calculated by subtracting the Baseline value from the individual post-Baseline (Day 7, Day 14, Day 28 and Day 42) values. If either the Baseline or post-Baseline value was missing, the change from Baseline was set to be missing. (NCT01725126)
Timeframe: Baseline (Day 1, Randomization) up to Day 42

,
Interventiong/L (Mean)
Albumin, Day 7Albumin, Day 14Albumin, Day 28Albumin, Day 42Total protein, Day 7Total protein, Day 14Total protein, Day 28Total protein, Day 42
Part A-GSK2890457-0.30.40.40.0-2.1-1.2-2.2-3.1
Part A-Placebo0.02.02.52.5-0.8-0.31.00.8

Change From Baseline in Clinical Chemistry Parameters of Albumin and Total Protein During the Double-blind Treatment Period of Part B and C

The assessments were done pre-dose at Day -1, Day 7, Day 14, Day 28 and Day 42. Baseline value was defined as the assessment done on Day -1. Change from Baseline was calculated by subtracting the Baseline value from the individual post-Baseline (Day 7, Day 14, Day 28 and Day 42) values. If either the Baseline or post-Baseline value was missing, the change from Baseline was set to be missing. (NCT01725126)
Timeframe: Baseline (Day -1) up to Day 42

,,,
Interventiong/L (Mean)
Albumin, Day 7Albumin, Day 14Albumin, Day 28Albumin, Day 42Total protein, Day 7Total protein, Day 14Total protein, Day 28Total protein, Day 42
Part B-GSK2890457+Liraglutide3.12.62.80.42.92.73.2-0.6
Part B-Placebo+Liraglutide2.02.71.80.03.04.03.20.5
Part C-GSK2890457+Metformin0.51.61.9-1.31.12.23.1-1.5
Part C-Placebo+Metformin1.30.82.3-0.81.01.72.8-0.7

Change From Baseline in Clinical Chemistry Parameters of Alkaline Phosphatase (ALP), ALT, Aspartate Aminotransferase (AST) and Gamma Glutamyltransferase (GGT) During Double-blind Treatment Period of Part A

The assessments were done pre-dose at Day 1, Day 7, Day 14, Day 28 and Day 42. Baseline value was defined as the assessment done on Day 1. Change from Baseline was calculated by subtracting the Baseline value from the individual post-Baseline (Day 7, Day 14, Day 28 and Day 42) values. If either the Baseline or post-Baseline value was missing, the change from Baseline was set to be missing. (NCT01725126)
Timeframe: Baseline (Day 1, Randomization) up to Day 42

,
InterventionInternational unit per liter (IU/L) (Mean)
ALP, Day 7ALP, Day 14ALP, Day 28ALP, Day 42ALT, Day 7ALT, Day 14ALT, Day 28ALT, Day 42AST, Day 7AST, Day 14AST, Day 28AST, Day 42GGT, Day 7GGT, Day 14GGT, Day 28GGT, Day 42
Part A-GSK2890457-3.8-1.4-1.8-1.8-4.1-4.4-8.2-7.7-0.41.4-3.1-0.3-0.1-0.1-2.9-0.5
Part A-Placebo-6.0-1.30.0-1.05.51.32.05.32.3-2.3-0.82.31.51.00.82.5

Change From Baseline in Clinical Chemistry Parameters of ALP, ALT, AST and GGT During the Double-blind Treatment Period of Part B and C

The assessments were done pre-dose at Day -1, Day 7, Day 14, Day 28 and Day 42. Baseline value was defined as the assessment done on Day -1. Change from Baseline was calculated by subtracting the Baseline value from the individual post-Baseline (Day 7, Day 14, Day 28 and Day 42) values. If either the Baseline or post-Baseline value was missing, the change from Baseline was set to be missing. (NCT01725126)
Timeframe: Baseline (Day -1) up to Day 42

,,,
InterventionIU/L (Mean)
ALP, Day 7ALP, Day 14ALP, Day 28ALP, Day 42ALT, Day 7ALT, Day 14ALT, Day 28ALT, Day 42AST, Day 7AST, Day 14AST, Day 28AST, Day 42GGT, Day 7GGT, Day 14GGT, Day 28GGT, Day 42
Part B-GSK2890457+Liraglutide5.51.82.82.2-0.10.60.91.01.11.92.23.8-1.2-1.40.80.2
Part B-Placebo+Liraglutide5.35.2-0.34.3-1.3-2.3-2.5-4.3-1.2-1.3-2.0-3.80.70.80.0-0.7
Part C-GSK2890457+Metformin-2.2-3.7-2.5-2.8-1.0-6.3-3.8-4.20.2-0.31.41.91.32.30.5-0.9
Part C-Placebo+Metformin1.86.76.30.51.53.00.7-0.5-0.5-1.00.71.00.35.32.3-0.7

Change From Baseline in Clinical Chemistry Parameters of Amylase and Lipase the Double-blind Treatment Period of Part B of Study

The assessments were done pre-dose at Day -1 and Day 42. Baseline value was defined as the assessment done on Day -1. Change from Baseline was calculated by subtracting the Baseline value from the individual post-Baseline (Day 42) value. If either the Baseline or post-Baseline value was missing, the change from Baseline was set to be missing. (NCT01725126)
Timeframe: Baseline (Day -1) and Day 42

,
InterventionUnits (U)/L (Mean)
Amylase, Day 42Lipase, Day 42
Part B-GSK2890457+Liraglutide9.218.8
Part B-Placebo+Liraglutide6.07.5

Change From Baseline in Clinical Chemistry Parameters of Direct Bilirubin, Total Bilirubin, Creatinine and Uric Acid During the Double-blind Treatment Period of Part A

The assessments were done pre-dose at Day 1, Day 7, Day 14, Day 28 and Day 42. Baseline value was defined as the assessment done on Day 1. Change from Baseline was calculated by subtracting the Baseline value from the individual post-Baseline (Day 7, Day 14, Day 28 and Day 42) values. If either the Baseline or post-Baseline value was missing, the change from Baseline was set to be missing. (NCT01725126)
Timeframe: Baseline (Day 1, Randomization) up to Day 42

,
InterventionMicromoles (umol)/L (Mean)
Direct bilirubin, Day 7Direct bilirubin, Day 14Direct bilirubin, Day 28Direct bilirubin, Day 42Total bilirubin, Day 7Total bilirubin, Day 14Total bilirubin, Day 28Total bilirubin, Day 42Creatinine, Day 7Creatinine, Day 14Creatinine, Day 28Creatinine, Day 42Uric acid, Day 7Uric acid, Day 14Uric acid, Day 28Uric acid, Day 42
Part A-GSK2890457-0.311-0.466-0.855-0.171-0.777-0.933-2.5650.513-6.4-4.8-7.1-8.8-10.3-17.84.2-26.2
Part A-Placebo0.0000.428-0.428-0.8550.0000.4281.2830.8552.2-4.40.0-2.2-7.4-14.9-1.5-7.4

Change From Baseline in Clinical Chemistry Parameters of Direct Bilirubin, Total Bilirubin, Creatinine and Uric Acid During the Double-blind Treatment Period of Part B and C

The assessments were done pre-dose at Day -1, Day 7, Day 14, Day 28 and Day 42. Baseline value was defined as the assessment done on Day -1. Change from Baseline was calculated by subtracting the Baseline value from the individual post-Baseline (Day 7, Day 14, Day 28 and Day 42) values. If either the Baseline or post-Baseline value was missing, the change from Baseline was set to be missing. (NCT01725126)
Timeframe: Baseline (Day -1) up to Day 42

,,,
Interventionumol/L (Mean)
Direct bilirubin, Day 7Direct bilirubin, Day 14Direct bilirubin, Day 28Direct bilirubin, Day 42Total bilirubin, Day 7Total bilirubin, Day 14Total bilirubin, Day 28Total bilirubin, Day 42Creatinine, Day 7Creatinine, Day 14Creatinine, Day 28Creatinine, Day 42Uric acid, Day 7Uric acid, Day 14Uric acid, Day 28Uric acid, Day 42
Part B-GSK2890457+Liraglutide-0.208-0.305-0.197-0.197-0.855-0.6110.1320.2633.04.22.0-2.425.115.316.97.8
Part B-Placebo+Liraglutide0.5420.3140.5130.5990.570-0.570-0.000-1.4254.6-0.11.9-1.015.9-11.92.0-5.0
Part C-GSK2890457+Metformin-0.200-0.185-0.014-0.3280.0000.2850.998-0.4283.44.68.2-0.89.925.334.70.5
Part C-Placebo+Metformin-0.513-0.086-0.171-0.200-3.705-0.855-0.855-0.2856.95.74.90.63.0-21.8-13.99.9

Change From Baseline in Clinical Chemistry Parameters of Electrolytes, Glucose Phosphorus Inorganic and Urea/Blood Urea Nitrogen (BUN) During the Double-blind Treatment Period of Part A

The electrolytes include calcium, chloride, carbon dioxide content/bicarbonate, potassium, magnesium and sodium. Assessments were done pre-dose at on Day 1, Day 7, Day 14, Day 28 and Day 42. Baseline value was defined as the assessment done on Day 1. Change from Baseline was calculated by subtracting the Baseline value from the individual post-Baseline (Day 7, Day 14, Day 28 and Day 42) values. If either the Baseline or post-Baseline value was missing, the change from Baseline was set to be missing. (NCT01725126)
Timeframe: Baseline (Day 1, Randomization) up to Day 42

,
InterventionMillimoles (mmol)/L (Mean)
Calcium, Day 7Calcium, Day 14Calcium, Day 28Calcium, Day 42Chloride, Day 7Chloride, Day 14Chloride, Day 28Chloride, Day 42Carbon dioxide/Bicarbonate, Day 7Carbon dioxide/Bicarbonate, Day 14Carbon dioxide/Bicarbonate, Day 28Carbon dioxide/Bicarbonate, Day 42Glucose, Day 7Glucose, Day 14Glucose, Day 28Glucose, Day 42Potassium, Day 7Potassium, Day 14Potassium, Day 28Potassium, Day 42Magnesium, Day 7Magnesium, Day 14Magnesium, Day 28Magnesium, Day 42Sodium, Day 7Sodium, Day 14Sodium, Day 28Sodium, Day 42Urea/BUN, Day 7Urea/BUN, Day 14Urea/BUN, Day 28Urea/BUN, Day 42Phosphorus inorganic, Day 7Phosphorus inorganic, Day 14Phosphorus inorganic, Day 28Phosphorus inorganic, Day 42
Part A-GSK2890457-0.023-0.023-0.010-0.0221.20.40.50.4-1.2-1.9-1.2-2.8-0.1-0.3-0.2-0.3-0.15-0.15-0.13-0.16-0.0299-0.0486-0.0288-0.02470.8-0.21.9-0.6-0.325-0.746-0.643-0.678-0.04-0.05-0.09-0.03
Part A-Placebo-0.0250.0560.0560.0500.81.0-1.5-0.80.3-1.0-0.5-2.5-0.0-0.0-0.1-0.20.150.20-0.070.30-0.0206-0.0617-0.0411-0.03080.3-0.31.0-1.3-0.179-0.268-0.536-0.625-0.07-0.14-0.020.01

Change From Baseline in Clinical Chemistry Parameters of Electrolytes, Glucose Phosphorus Inorganic, BUN and Cholesterol During the Double-blind Treatment Period of Part B and C

The electrolytes include calcium, chloride, carbon dioxide content/bicarbonate, potassium, magnesium and sodium. Assessments were done pre-dose at Day -1, Day 7, Day 14, Day 28 and Day 42. Baseline value was defined as the assessment done on Day -1. Change from Baseline was calculated by subtracting the Baseline value from the individual post-Baseline (Day 7, Day 14, Day 28 and Day 42) values. If either the Baseline or post-Baseline value was missing, the change from Baseline was set to be missing. (NCT01725126)
Timeframe: Baseline (Day -1) up to Day 42

,,,
Interventionmmol/L (Mean)
Calcium, Day 7Calcium, Day 14Calcium, Day 28Calcium, Day 42Chloride, Day 7Chloride, Day 14Chloride, Day 28Chloride, Day 42Carbon dioxide/Bicarbonate, Day 7Carbon dioxide/Bicarbonate, Day 14Carbon dioxide/Bicarbonate, Day 28Carbon dioxide/Bicarbonate, Day 42Glucose, Day 7Glucose, Day 14Glucose, Day 28Glucose, Day 42Potassium, Day 7Potassium, Day 14Potassium, Day 28Potassium, Day 42Magnesium, Day 7Magnesium, Day 14Magnesium, Day 28Magnesium, Day 42Sodium, Day 7Sodium, Day 14Sodium, Day 28Sodium, Day 42Urea/BUN, Day 7Urea/BUN, Day 14Urea/BUN, Day 28Urea/BUN, Day 42Cholesterol, Day 42Phosphorus inorganic, Day 7Phosphorus inorganic, Day 14Phosphorus inorganic, Day 28Phosphorus inorganic, Day 42
Part B-GSK2890457+Liraglutide0.0530.0410.046-0.040-1.2-0.10.20.2-2.0-1.9-0.4-1.80.30.2-0.2-0.10.090.200.080.010.02940.01760.03790.00630.21.41.7-0.40.3830.1280.302-0.412-0.1030.010.05-0.01-0.04
Part B-Placebo+Liraglutide0.0830.0500.021-0.025-1.5-0.80.8-1.00.0-1.8-1.00.5-0.3-0.1-0.10.20.330.170.28-0.050.0206-0.02060.0274-0.01371.21.31.80.5-0.000-0.2970.119-0.595-0.8530.100.010.060.01
Part C-GSK2890457+Metformin-0.0040.0170.035-0.0560.40.60.30.3-0.6-0.7-0.3-1.3-1.7-2.2-2.00.10.060.07-0.070.08-0.02060.02060.0240-0.01710.81.50.6-1.0-0.208-0.2680.863-0.387-0.1550.010.030.12-0.00
Part C-Placebo+Metformin0.0250.0670.004-0.0710.80.51.00.5-2.0-2.0-2.3-2.80.90.51.51.20.280.170.10-0.050.02060.00690.0411-0.02741.31.51.0-1.00.1790.1780.714-0.655-0.052-0.03-0.10-0.12-0.05

Change From Baseline in Clinical Chemistry Parameters of Insulin During the Double-blind Treatment Period of Part A

The assessments were done pre-dose at Day 1, Day 7, Day 14, Day 28 and Day 42. Baseline value was defined as the assessment done on Day 1. Change from Baseline was calculated by subtracting the Baseline value from the individual post-Baseline (Day 7, Day 14, Day 28 and Day 42) values. If either the Baseline or post-Baseline value was missing, the change from Baseline was set to be missing. (NCT01725126)
Timeframe: Baseline (Day 1, Randomization) up to Day 42

,
InterventionPicomoles (pmol)/L (Mean)
Day 7Day 14Day 28Day 42
Part A-GSK289045712.5161.9738.969-13.735
Part A-Placebo-1.2568.072-11.659-22.721

Change From Baseline in Clinical Chemistry Parameters of Insulin During the Double-blind Treatment Period of Part B and C

The assessments were done pre-dose at Day -1, Day 7, Day 14, Day 28 and Day 42. Baseline value was defined as the assessment done on Day -1. Change from Baseline was calculated by subtracting the Baseline value from the individual post-Baseline (Day 7, Day 14, Day 28 and Day 42) values. If either the Baseline or post-Baseline value was missing, the change from Baseline was set to be missing. (NCT01725126)
Timeframe: Baseline (Day -1) up to Day 42

,,,
Interventionpmol/L (Mean)
Day 7Day 14Day 28Day 42
Part B-GSK2890457+Liraglutide-20.05-9.62-35.18-8.12
Part B-Placebo+Liraglutide-20.21-21.65-53.41-12.99
Part C-GSK2890457+Metformin-29.59-41.14-7.2235.28
Part C-Placebo+Metformin45.11-79.3934.2834.28

Change From Baseline in Clinical Chemistry Parameters of Thyroid Stimulating Hormone During the Double-blind Treatment Period of Part B and C

The assessments were done pre-dose at Day -1, Day 7 and Day 42. Baseline value was defined as the assessment done Day -1. Change from Baseline was calculated by subtracting the Baseline value from the individual post-Baseline (Day 7 and Day 42) values. If either the Baseline or post-Baseline value was missing, the change from Baseline was set to be missing. (NCT01725126)
Timeframe: Baseline (Day -1) up to Day 42

,,
InterventionMilliunits (mu/L) (Mean)
Day 42
Part B-Placebo+Liraglutide0.137
Part C-GSK2890457+Metformin0.149
Part C-Placebo+Metformin-0.187

Change From Baseline in Clinical Chemistry Parameters of Thyroid Stimulating Hormone During the Double-blind Treatment Period of Part B and C

The assessments were done pre-dose at Day -1, Day 7 and Day 42. Baseline value was defined as the assessment done Day -1. Change from Baseline was calculated by subtracting the Baseline value from the individual post-Baseline (Day 7 and Day 42) values. If either the Baseline or post-Baseline value was missing, the change from Baseline was set to be missing. (NCT01725126)
Timeframe: Baseline (Day -1) up to Day 42

InterventionMilliunits (mu/L) (Mean)
Day 7Day 42
Part B-GSK2890457+Liraglutide-5.790-0.067

Change From Baseline in Clinical Chemistry Parameters of Total Thyroxine and Total T3 During the Double-blind Treatment Period of Part B and C

The assessments were done pre-dose at Day -1 and Day 42. Baseline value was defined as the assessment done Day -1. Change from Baseline was calculated by subtracting the Baseline value from the individual post-Baseline (Day 42) value. If either the Baseline or post-Baseline value was missing, the change from Baseline was set to be missing. (NCT01725126)
Timeframe: Baseline (Day -1) and Day 42

,,,
InterventionNanomoles (nmol)/L (Mean)
Total thyroxineTotal T3
Part B-GSK2890457+Liraglutide1.08910.1
Part B-Placebo+Liraglutide0.8578-0.3
Part C-GSK2890457+Metformin-2.3597-0.2
Part C-Placebo+Metformin-5.1478-0.2

Change From Baseline in ECG Intervals During Part B and C

Single 12-lead ECGs was obtained after participants rested in a supine position for at least 10 minutes using an ECG machine that automatically calculated the HR and measured PR, QRS, QT, QTcB, QTcF and RR intervals. The assessments were done at Day -1 (pre-dose, triplicate), Day 42 (pre-dose) and Follow-up Visit. Baseline value was defined as the average of the triplicate pre-dose assessments done on Day -1. Change from Baseline was calculated by subtracting the Baseline value from the individual post-Baseline (Day 42 and Follow-up) values. If either the Baseline or post-Baseline value was missing, the change from Baseline was set to be missing. (NCT01725126)
Timeframe: Baseline (Day -1) up to Follow-up (Day 56)

,,,
InterventionMilliseconds (Mean)
PR Interval, Day 42PR Interval, Follow-upQRS Duration, Day 42QRS Duration, Follow-upQT Interval, Day 42QT Interval, Follow-upQTcB, Day 42QTcB, Follow-upQTcF, Day 42QTcF, Follow-upRR Interval, Day 42RR Interval, Follow-up
Part B-GSK2890457+Liraglutide3.08-3.69-2.62-1.69-1.69-5.69-1.51-10.95-1.49-9.10-0.000.02
Part B-Placebo+Liraglutide5.56-1.110.780.118.111.44-2.87-5.891.17-3.170.040.03
Part C-GSK2890457+Metformin-4.44-6.28-1.060.110.78-5.56-4.23-2.14-2.58-3.500.02-0.01
Part C-Placebo+Metformin-6.44-3.110.110.782.780.780.43-3.201.22-1.780.010.02

Change From Baseline in Electrocardiogram (ECG) Intervals During Part A

Single 12-lead ECGs was obtained after participants rested in a supine position for at least 10 minutes using an ECG machine that automatically calculated the HR and measured PR, QRS, QT, QT duration corrected for HR by Fridericia's formula (QTcF) and QT duration corrected for HR by Bazett's formula (QTcB intervals. The assessments were done at Day 1 (pre-dose, triplicate), Day 42 (pre-dose) and Follow-up Visit. Baseline value was defined as the average of the triplicate pre-dose assessments done on Day 1. Change from Baseline was calculated by subtracting the Baseline value from the individual post-Baseline (Day 42 and Follow-up) values. If either the Baseline or post-Baseline value was missing, the change from Baseline was set to be missing. (NCT01725126)
Timeframe: Baseline (Day 1, Randomization) up to Follow-up (Day 56)

,
InterventionMilliseconds (Mean)
PR Interval, Day 42PR Interval, Follow-upQRS Duration, Day 42QRS Duration, Follow-upQT Interval, Day 42QT Interval, Follow-upQTcB, Day 42QTcB, Follow-upQTcF, Day 42QTcF, Follow-up
Part A-GSK28904571.11.5-2.1-0.716.4-10.2-3.36.33.20.7
Part A-Placebo6.39.02.23.910.80.38.26.99.14.8

Change From Baseline in Fasting Insulin and Weighted Mean Insulin AUC (0-4 Hour) and AUC (0-24 Hour) During the Double-blind Treatment Period of Part B and C

Two fasting samples 5 minutes apart were taken for insulin. Baseline insulin level was the average of the 2 fasting samples. For insulin weighted mean AUC (0-4 hour) and weighted mean AUC (0-24 hour) was calculated for Baseline (Day -1) and end of treatment (Day 42). AUC was calculated using the linear trapezoid method that is the sum of the areas between each chronological pair of assessments at the time points (at Day -1 and Day 42). The weighted mean was then calculated by dividing the AUC by the length of the time interval over which it was calculated. Baseline was defined as the assessment done on Day -1. Change from Baseline was calculated by subtracting the Baseline (Day -1) values from the post-Baseline value (Day 42). Data is reported for weighted mean insulin AUC (0-4 hour) post-breakfast and AUC (0-24 hour) post-breakfast. (NCT01725126)
Timeframe: Baseline (Day -1) and Day 42

,,,
Interventionpmol/L (Mean)
Fasting InsulinInsulin Weighted Mean AUC 0-4 hourInsulin Weighted Mean AUC 0-24 hour
Part B-GSK2890457+Liraglutide1.13314.589-13.905
Part B-Placebo+Liraglutide-4.88769.6351.626
Part C-GSK2890457+Metformin12.30010.32217.134
Part C-Placebo+Metformin-11.94657.88722.740

Change From Baseline in Fasting Plasma Glucose (Safety Laboratory) Values During the Double-blind Treatment Period of Part B and C

The assessments were done at Day -1, Day 7, Day 14, Day 28, Day 42 and Follow-up Visit. Baseline was defined as the assessment done on Day -1. Change from Baseline was calculated by subtracting the Baseline (Day -1) values from the post-Baseline (Day 7, 14, 28, 42 and Follow-up visit) values. (NCT01725126)
Timeframe: Baseline (Day -1) up to Follow-up (Day 56)

,,,
Interventionmmol/L (Mean)
Day 7Day 14Day 28Day 42Follow-up
Part B-GSK2890457+Liraglutide0.2850.210-0.201-0.0980.444
Part B-Placebo+Liraglutide-0.278-0.093-0.1110.1940.962
Part C-GSK2890457+Metformin-1.665-2.216-1.9890.074-1.226
Part C-Placebo+Metformin0.8790.5181.5361.1841.249

Change From Baseline in Hematology Parameter of Hematocrit During the Double-blind Treatment Period of Part A

The assessments were done pre-dose at Day 1, Day 7, Day 14, Day 28 and Day 42. Baseline value was defined as the assessment done on Day 1. Change from Baseline was calculated by subtracting the Baseline value from the individual post-Baseline (Day 7, Day 14, Day 28 and Day 42) values. If either the Baseline or post-Baseline value was missing, the change from Baseline was set to be missing. (NCT01725126)
Timeframe: Baseline (Day 1, Randomization) up to Day 42

,
InterventionRatio (Mean)
Day 7Day 14Day 28Day 42
Part A-GSK2890457-0.0128-0.0026-0.0066-0.0089
Part A-Placebo0.00000.01280.02280.0060

Change From Baseline in Hematology Parameter of Hematocrit During the Double-blind Treatment Period of Part B and C

The assessments were done pre-dose at Day -1, Day 7, Day 14, Day 28 and Day 42. Baseline value was defined as the assessment done on Day -1. Change from Baseline was calculated by subtracting the Baseline value from the individual post-Baseline (Day 7, Day 14, Day 28 and Day 42) values. If either the Baseline or post-Baseline value was missing, the change from Baseline was set to be missing. (NCT01725126)
Timeframe: Baseline (Day -1) up to Day 42

,,,
InterventionRatio (Mean)
Day 7Day 14Day 28Day 42
Part B-GSK2890457+Liraglutide0.00190.0011-0.0003-0.0025
Part B-Placebo+Liraglutide0.0032-0.0028-0.0003-0.0022
Part C-GSK2890457+Metformin-0.0072-0.00360.0003-0.0159
Part C-Placebo+Metformin-0.00820.0057-0.0010-0.0087

Change From Baseline in Hematology Parameter of MCH During the Double-blind Treatment Period of Part B and C

The assessments were done pre-dose at Day -1, Day 7, Day 14, Day 28 and Day 42. Baseline value was defined as the assessment done on Day -1. Change from Baseline was calculated by subtracting the Baseline value from the individual post-Baseline (Day 7, Day 14, Day 28 and Day 42) values. If either the Baseline or post-Baseline value was missing, the change from Baseline was set to be missing. (NCT01725126)
Timeframe: Baseline (Day -1) up to Day 42

,,,
InterventionPicograms (Mean)
Day 7Day 14Day 28Day 42
Part B-GSK2890457+Liraglutide-0.21-0.100.010.08
Part B-Placebo+Liraglutide-0.020.180.17-0.12
Part C-GSK2890457+Metformin-0.180.03-0.080.02
Part C-Placebo+Metformin-0.23-0.25-0.20-0.28

Change From Baseline in Hematology Parameter of MCV During the Double-blind Treatment Period of Part B and C

The assessments were done pre-dose at Day -1, Day 7, Day 14, Day 28 and Day 42. Baseline value was defined as the assessment done on Day -1. Change from Baseline was calculated by subtracting the Baseline value from the individual post-Baseline (Day 7, Day 14, Day 28 and Day 42) values. If either the Baseline or post-Baseline value was missing, the change from Baseline was set to be missing. (NCT01725126)
Timeframe: Baseline (Day -1) up to Day 42

,,,
InterventionFemtoliters (Mean)
Day 7Day 14Day 28Day 42
Part B-GSK2890457+Liraglutide0.390.540.550.07
Part B-Placebo+Liraglutide0.350.020.05-0.90
Part C-GSK2890457+Metformin0.250.760.17-0.27
Part C-Placebo+Metformin0.40-0.47-0.18-0.78

Change From Baseline in Hematology Parameter of Mean Corpuscle Hemoglobin (MCH) During the Double-blind Treatment Period of Part A

The assessments were done pre-dose at Day 1, Day 7, Day 14, Day 28 and Day 42. Baseline value was defined as the assessment done on Day 1. Change from Baseline was calculated by subtracting the Baseline value from the individual post-Baseline (Day 7, Day 14, Day 28 and Day 42) values. If either the Baseline or post-Baseline value was missing, the change from Baseline was set to be missing. (NCT01725126)
Timeframe: Baseline (Day 1, Randomization) up to Day 42

,
InterventionPicograms (Mean)
Day 7Day 14Day 28Day 42
Part A-GSK28904570.310.320.370.89
Part A-Placebo0.250.270.701.40

Change From Baseline in Hematology Parameter of Mean Corpuscle Volume (MCV) During the Double-blind Treatment Period of Part A

The assessments were done pre-dose at Day 1, Day 7, Day 14, Day 28 and Day 42. Baseline value was defined as the assessment done on Day 1. Change from Baseline was calculated by subtracting the Baseline value from the individual post-Baseline (Day 7, Day 14, Day 28 and Day 42) values. If either the Baseline or post-Baseline value was missing, the change from Baseline was set to be missing. (NCT01725126)
Timeframe: Baseline (Day 1, Randomization) up to Day 42

,
InterventionFemtoliters (Mean)
Day 7Day 14Day 28Day 42
Part A-GSK2890457-0.550.95-0.620.35
Part A-Placebo0.150.85-0.30-0.90

Change From Baseline in Hematology Parameters of Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count, WBC Count During the Double-blind Treatment Period of Part B and C

The assessments were done pre-dose at Day -1, Day 7, Day 14, Day 28 and Day 42. Baseline value was defined as the assessment done on Day -1. Change from Baseline was calculated by subtracting the Baseline value from the individual post-Baseline (Day 7, Day 14, Day 28 and Day 42) values. If either the Baseline or post-Baseline value was missing, the change from Baseline was set to be missing. (NCT01725126)
Timeframe: Baseline (Day -1) up to Day 42

,,,
InterventionGI/L (Mean)
Basophils, Day 7Basophils, Day 14Basophils, Day 28Basophils, Day 42Eosinophils, Day 7Eosinophils, Day 14Eosinophils, Day 28Eosinophils, Day 42Lymphocytes, Day 7Lymphocytes, Day 14Lymphocytes, Day 28Lymphocytes, Day 42Monocytes, Day 7Monocytes, Day 14Monocytes, Day 28Monocytes, Day 42Total Neutrophils, Day 7Total Neutrophils, Day 14Total Neutrophils, Day 28Total Neutrophils, Day 42Platelet count, Day 7Platelet count, Day 14Platelet count, Day 28Platelet count, Day 42WBC count, Day 7WBC count, Day 14WBC count, Day 28WBC count, Day 42
Part B-GSK2890457+Liraglutide0.00470.00410.00500.00190.040.030.020.060.110.040.05-0.11-0.01-0.04-0.03-0.06-0.13-0.19-0.17-0.148.97.010.8-13.2-0.01-0.17-0.13-0.26
Part B-Placebo+Liraglutide0.02700.0037-0.00020.00980.020.010.010.010.310.180.080.020.04-0.050.030.000.270.38-0.01-0.2418.312.84.5-2.00.650.520.08-0.20
Part C-GSK2890457+Metformin-0.0078-0.0066-0.0068-0.0122-0.03-0.00-0.00-0.010.140.180.25-0.070.000.060.03-0.030.380.640.36-0.105.812.910.4-15.30.480.880.63-0.22
Part C-Placebo+Metformin0.0047-0.0015-0.0065-0.0190-0.01-0.020.01-0.020.090.080.05-0.110.010.060.06-0.00-0.54-0.27-0.48-0.505.01.20.5-13.8-0.43-0.13-0.35-0.62

Change From Baseline in Hematology Parameters of Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count, White Blood Cell (WBC) Count During the Double-blind Treatment Period of Part A

The assessments were done pre-dose at Day 1, Day 7, Day 14, Day 28 and Day 42. Baseline value was defined as the assessment done on Day 1. Change from Baseline was calculated by subtracting the Baseline value from the individual post-Baseline (Day 7, Day 14, Day 28 and Day 42) values. If either the Baseline or post-Baseline value was missing, the change from Baseline was set to be missing. (NCT01725126)
Timeframe: Baseline (Day 1, Randomization) up to Day 42

,
InterventionGiga cells (GI)/L (Mean)
Basophils, Day 7Basophils, Day 14Basophils, Day 28Basophils, Day 42Eosinophils, Day 7Eosinophils, Day 14Eosinophils, Day 28Eosinophils, Day 42Lymphocytes, Day 7Lymphocytes, Day 14Lymphocytes, Day 28Lymphocytes, Day 42Monocytes, Day 7Monocytes, Day 14Monocytes, Day 28Monocytes, Day 42Total Neutrophils, Day 7Total Neutrophils, Day 14Total Neutrophils, Day 28Total Neutrophils, Day 42Platelet count, Day 7Platelet count, Day 14Platelet count, Day 28Platelet count, Day 42WBC count, Day 7WBC count, Day 14WBC count, Day 28WBC count, Day 42
Part A-GSK28904570.000.010.000.00-0.030.000.000.00-0.01-0.06-0.320.05-0.05-0.050.01-0.060.02-0.130.14-0.01-1.93.89.73.1-0.11-0.15-0.16-0.01
Part A-Placebo0.00-0.030.000.00-0.03-0.030.100.03-0.22-0.22-0.230.15-0.08-0.10-0.05-0.050.150.50-0.320.48-4.8-14.0-11.5-8.8-0.150.18-0.500.65

Change From Baseline in Hematology Parameters of Hemoglobin and MCHC During the Double-blind Treatment Period of Part B and C

The assessments were done pre-dose at Day -1, Day 7, Day 14, Day 28 and Day 42. Baseline value was defined as the assessment done on Day -1. Change from Baseline was calculated by subtracting the Baseline value from the individual post-Baseline (Day 7, Day 14, Day 28 and Day 42) values. If either the Baseline or post-Baseline value was missing, the change from Baseline was set to be missing. (NCT01725126)
Timeframe: Baseline (Day -1) up to Day 42

,,,
Interventiong/L (Mean)
Hemoglobin, Day 7Hemoglobin, Day 14Hemoglobin, Day 28Hemoglobin, Day 42MCHC, Day 7MCHC, Day 14MCHC, Day 28MCHC, Day 42
Part B-GSK2890457+Liraglutide-1.0-1.1-1.1-0.8-4.1-3.8-1.90.2
Part B-Placebo+Liraglutide0.20.20.30.0-2.02.01.72.0
Part C-GSK2890457+Metformin-3.4-2.1-0.3-4.8-2.8-2.6-1.40.8
Part C-Placebo+Metformin-4.31.7-1.2-2.8-4.5-1.2-2.0-0.2

Change From Baseline in Hematology Parameters of Hemoglobin and Mean Corpuscle Hemoglobin Concentration (MCHC) During the Double-blind Treatment Period of Part A

The assessments were done pre-dose at Day 1, Day 7, Day 14, Day 28 and Day 42. Baseline value was defined as the assessment done on Day 1. Change from Baseline was calculated by subtracting the Baseline value from the individual post-Baseline (Day 7, Day 14, Day 28 and Day 42) values. If either the Baseline or post-Baseline value was missing, the change from Baseline was set to be missing. (NCT01725126)
Timeframe: Baseline (Day 1, Randomization) up to Day 42

,
Interventiong/L (Mean)
Hemoglobin, Day 7Hemoglobin, Day 14Hemoglobin, Day 28Hemoglobin, Day 42MCHC, Day 7MCHC, Day 14MCHC, Day 28MCHC, Day 42
Part A-GSK2890457-2.0-0.90.50.95.40.06.39.0
Part A-Placebo0.84.011.39.81.8-0.58.517.5

Change From Baseline in Hematology Parameters of RBC Count and Reticulocytes During the Double-blind Treatment Period of Part B and C

The assessments were done pre-dose at Day -1, Day 7, Day 14, Day 28 and Day 42. Baseline value was defined as the assessment done on Day -1. Change from Baseline was calculated by subtracting the Baseline value from the individual post-Baseline (Day 7, Day 14, Day 28 and Day 42) values. If either the Baseline or post-Baseline value was missing, the change from Baseline was set to be missing. (NCT01725126)
Timeframe: Baseline (Day -1) up to Day 42

,,,
InterventionTI/L (Mean)
RBC count, Day 7RBC count, Day 14RBC count, Day 28RBC count, Day 42Reticulocytes, Day 7Reticulocytes, Day 14Reticulocytes, Day 28Reticulocytes, Day 42
Part B-GSK2890457+Liraglutide0.004-0.011-0.023-0.031-0.00030.00950.00350.0096
Part B-Placebo+Liraglutide0.018-0.0300.0020.0320.0020-0.00190.00290.0062
Part C-GSK2890457+Metformin-0.085-0.072-0.003-0.168-0.00150.0147-0.0052-0.0042
Part C-Placebo+Metformin-0.1070.0930.020-0.053-0.0210-0.0286-0.0304-0.0200

Change From Baseline in Hematology Parameters of Red Blood Cell (RBC) Count and Reticulocytes During the Double-blind Treatment Period of Part A

The assessments were done pre-dose at Day 1, Day 7, Day 14, Day 28 and Day 42. Baseline value was defined as the assessment done on Day 1. Change from Baseline was calculated by subtracting the Baseline value from the individual post-Baseline (Day 7, Day 14, Day 28 and Day 42) values. If either the Baseline or post-Baseline value was missing, the change from Baseline was set to be missing. (NCT01725126)
Timeframe: Baseline (Day 1, Randomization) up to Day 42

,
InterventionTrillion cells (TI)/L (Mean)
RBC count, Day 7RBC count, Day 14RBC count, Day 28RBC count, Day 42Reticulocytes, Day 7Reticulocytes, Day 14Reticulocytes, Day 28Reticulocytes, Day 42
Part A-GSK2890457-0.116-0.084-0.045-0.1150.0014-0.00170.00710.0044
Part A-Placebo-0.0080.0900.2580.1070.01150.00770.00730.0022

Change From Baseline in In-clinic Body Weight During the Double-blind Treatment Period of Part B and C

During the assessment of body weight in the unit, the participant wore lightweight indoor clothing and removed shoes. The assessments were done pre-dose at Day -1, Day 1, Day 7, Day 14, Day 28, Day 42 and Day 43. Baseline value was defined as the average of Day -1 and Day 1 values. Change from Baseline was calculated by subtracting the Baseline value from the individual post-Baseline (Day 7, Day 14, Day 28 and Day 42) values. If either the Baseline or post-Baseline value was missing, the change from Baseline was set to be missing. Day 42 value was the average of Day 42 and Day 43 values. (NCT01725126)
Timeframe: Baseline (Day -1 and Day 1) up to Day 42

,,,
InterventionKilograms (kg) (Mean)
Day 7Day 14Day 28Day 42
Part B-GSK2890457+Liraglutide0.200.050.47-0.39
Part B-Placebo+Liraglutide-0.120.370.15-0.74
Part C-GSK2890457+Metformin0.470.560.270.42
Part C-Placebo+Metformin0.280.610.52-0.47

Change From Baseline in the Overall Gastrointestinal (GI) Symptoms Rating Scale (GSRS) Score During the Double-blind Treatment Period of Part A

The impact of GI symptoms on health-related quality of life was assessed using the GSRS. The GSRS is a 15-item related to abdominal pain, reflux, indigestion, diarrhea and constipation syndromes, self-administered questionnaire that assesses the impact of gastrointestinal symptoms during the past week on a scale from 1 (no discomfort at all) to 7 (very severe discomfort). Overall GSRS was the mean of items 1 to 15. Possible overall scores range from 1 to 7, with lower scores indicating a better quality of life with respect to GI symptoms and higher scores indicating a lower quality of life with respect to GI symptoms. Baseline was defined as the assessment done on Day 1. Change from Baseline was calculated by subtracting the Baseline value from the individual post-Baseline (Day 7, 14 and 42) values. If either the Baseline or post-Baseline value was missing, the change from Baseline was set to be missing. (NCT01725126)
Timeframe: Baseline (Day 1, Randomization) up to Day 42

,
InterventionScores on scale (Mean)
Day 7Day 14Day 42
Part A-GSK28904570.080.04-0.02
Part A-Placebo0.020.080.02

Change From Baseline in the Overall GSRS Score During the Double-blind Treatment Period of Part B and C

The impact of GI symptoms on health-related quality of life was assessed using the GSRS. The GSRS is a 15-item related to abdominal pain, reflux, indigestion, diarrhea and constipation syndromes, self-administered questionnaire that assesses the impact of gastrointestinal symptoms during the past week on a scale from 1 (no discomfort at all) to 7 (very severe discomfort). Overall GSRS was the mean of items 1 to 15. Possible overall scores range from 1 to 7, with lower scores indicating a better quality of life with respect to GI symptoms and higher scores indicating a lower quality of life with respect to GI symptoms. Baseline was defined as the assessment done on Day -2. Change from Baseline was calculated by subtracting the Baseline value from the individual post-Baseline (Day 7, 14, 28 and 41) values. If either the Baseline or post-Baseline value was missing, the change from Baseline was set to be missing. (NCT01725126)
Timeframe: Baseline (Day -2) up to Day 41

,,,
InterventionScores on scale (Mean)
Day 7Day 14Day 28Day 41
Part B-GSK2890457+Liraglutide-0.030.050.03-0.12
Part B-Placebo+Liraglutide0.03-0.09-0.21-0.11
Part C-GSK2890457+Metformin0.130.280.270.10
Part C-Placebo+Metformin0.240.200.140.02

Change From Baseline in Vital Sign Parameter of Heart Rate (HR) During the Double-blind Treatment Period of Part A

Vital sign assessments were performed after resting in a supine or semi-supine position for at least 10 minutes. The assessments were done pre-dose at Day 1, Day 7, Day 14, Day 28 and Day 42. Baseline value was defined as the assessment done on Day 1. Change from Baseline was calculated by subtracting the Baseline value from the individual post-Baseline (Day 7, Day 14, Day 28 and Day 42) values. If either the Baseline or post-Baseline value was missing, the change from Baseline was set to be missing. (NCT01725126)
Timeframe: Baseline (Day 1, Randomization) up to Day 42

,
InterventionBeats per minute (Mean)
Day 7Day 14Day 28Day 42
Part A-GSK28904574.60.63.3-4.4
Part A-Placebo8.06.35.5-1.3

Change From Baseline in Vital Sign Parameter of HR During the Double-blind Treatment Period of Part B and C

Vital sign assessments were performed after resting in a supine or semi-supine position for at least 10 minutes. The assessments were done pre-dose at Day -1, Day 7, Day 14, Day 28 and Day 42. Baseline value was defined as the assessment done on Day -1. Change from Baseline was calculated by subtracting the Baseline value from the individual post-Baseline (Day 7, Day 14, Day 28 and Day 42) values. If either the Baseline or post-Baseline value was missing, the change from Baseline was set to be missing. (NCT01725126)
Timeframe: Baseline (Day -1) up to Day 42

,,,
InterventionBeats per minute (Mean)
Day 7Day 14Day 28Day 42
Part B-GSK2890457+Liraglutide0.30.43.71.6
Part B-Placebo+Liraglutide-3.6-3.3-7.8-4.8
Part C-GSK2890457+Metformin1.63.61.50.5
Part C-Placebo+Metformin0.10.81.8-3.2

Change From Baseline in Vital Sign Parameter of SBP and DBP During the Double-blind Treatment Period of Part B and C

Vital sign assessments were performed after resting in a supine or semi-supine position for at least 10 minutes. The assessments were done pre-dose at Day -1, Day 7, Day 14, Day 28 and Day 42. Baseline value was defined as the assessment done on Day -1. Change from Baseline was calculated by subtracting the Baseline value from the individual post-Baseline (Day 7, Day 14, Day 28 and Day 42) values. If either the Baseline or post-Baseline value was missing, the change from Baseline was set to be missing. (NCT01725126)
Timeframe: Baseline (Day -1) up to Day 42

,,,
InterventionmmHg (Mean)
SBP, Day 7SBP, Day 14SBP, Day 28SBP, Day 42DBP, Day 7DBP, Day 14DBP, Day 28DBP, Day 42
Part B-GSK2890457+Liraglutide2.03.60.20.10.40.80.40.8
Part B-Placebo+Liraglutide1.65.6-0.6-2.6-2.42.1-3.3-1.5
Part C-GSK2890457+Metformin-3.7-2.8-7.4-3.0-0.8-2.5-3.4-3.2
Part C-Placebo+Metformin3.23.24.50.00.9-0.8-0.41.1

Change From Baseline in Vital Sign Parameter of Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) During the Double-blind Treatment Period of Part A

Vital sign assessments were performed after resting in a supine or semi-supine position for at least 10 minutes. The assessments were done pre-dose at Day 1, Day 7, Day 14, Day 28 and Day 42. Baseline value was defined as the assessment done on Day 1. Change from Baseline was calculated by subtracting the Baseline value from the individual post-Baseline (Day 7, Day 14, Day 28 and Day 42) values. If either the Baseline or post-Baseline value was missing, the change from Baseline was set to be missing. (NCT01725126)
Timeframe: Baseline (Day 1, Randomization) up to Day 42

,
InterventionMillimeters of mercury (mmHg) (Mean)
SBP, Day 7SBP, Day 14SBP, Day 28SBP, Day 42DBP, Day 7DBP, Day 14DBP, Day 28DBP, Day 42
Part A-GSK2890457-4.0-3.9-5.5-7.5-6.2-5.0-8.4-6.4
Part A-Placebo0.8-0.5-3.3-1.0-5.3-1.8-1.3-0.8

Change From Baseline in Weighted Mean Glucose Area Under the Curves From Time 0 to 24 Hours (AUC [0-24 Hours]) During the Double-blind Treatment Period of Part B and C

AUC was calculated using the linear trapezoid method that is the sum of the areas between each chronological pair of assessments at the time points (at Day -1 and Day 42). The weighted mean was then calculated by dividing the AUC by the length of the time interval over which it was calculated. Baseline was defined as the assessment done on Day -1. Change from Baseline was calculated by subtracting the Baseline (Day -1) values from the post-Baseline value (Day 42). Data is reported for weighted mean glucose AUC (0-4 hour) post-breakfast and AUC (0-24 hour) post-breakfast. Adjusted mean is reported as least square (LS) mean. (NCT01725126)
Timeframe: Baseline (Day -1) and Day 42

,,,
Interventionmmol/L (Least Squares Mean)
AUC (0-4 hour)AUC (0-24 hour)
Part B-GSK2890457+Liraglutide-0.164-0.968
Part B-Placebo+Liraglutide0.018-0.613
Part C-GSK2890457+Metformin0.3410.156
Part C-Placebo+Metformin1.1941.376

Cmax of Metformin During the Double-blind Treatment Period of Part A

Blood samples were collected on Day 1 and 42 at pre-dose (0 hour), 15 minutes, 30 minutes, 1, 1.5, 2, 4 (pre-lunch), 5.5, 6, 8 and 10 (pre-dinner) hours post-dose. The first occurrence of the Cmax was determined directly from the raw concentration-time data. (NCT01725126)
Timeframe: Day 1 and Day 42 at pre-dose (0 hour), 15 minutes, 30 minutes, 1, 1.5, 2, 4, 5.5, 6, 8 and 10 hours post-dose

,
InterventionNanograms/mL (Geometric Mean)
Day 1Day 42
Part A-GSK2890457576.2374.1
Part A-Placebo681.8860.1

Maximum Observed Concentration (Cmax) of Liraglutide During the Double-blind Treatment Period of Part B

Blood samples were collected on Day -1 and 42 at pre-dose (0 hour), 15 minutes, 30 minutes, 1, 1.5, 2, 4 (pre-lunch), 5.5, 6, 8, 10 (pre-dinner), 11.5, 12, 14 and 24 hours post-dose. The first occurrence of the Cmax was determined directly from the raw concentration-time data. (NCT01725126)
Timeframe: Day -1 and 42 at pre-dose (0 hour), 15 minutes, 30 minutes, 1, 1.5, 2, 4, 5.5, 6, 8, 10, 11.5, 12, 14 and 24 hours post-dose

,
InterventionNanograms/mL (Geometric Mean)
Day -1Day 42
Part B-GSK2890457+Liraglutide72.2470.86
Part B-Placebo+Liraglutide120.00128.57

Mean pH Values of Urine During the Double-blind Treatment Period of Part A

Urinalysis parameter included urine pH. pH was calculated on a scale of 0 to 14, such that, the lower the number, more acidic the urine and higher the number, more alkaline the urine with 7 being neutral. The assessments were done pre-dose on Day 1, Day 7, Day 14, Day 28 and Day 42. (NCT01725126)
Timeframe: up to Day 42

,
InterventionpH (Mean)
Day 1Day 7Day 14Day 28Day 42
Part A-GSK28904575.955.865.916.056.20
Part A-Placebo5.255.885.506.135.63

Mean pH Values of Urine During the Double-blind Treatment Period of Part B and C

Urinalysis parameter included urine pH. pH was calculated on a scale of 0 to 14, such that, the lower the number, more acidic the urine and higher the number, more alkaline the urine with 7 being neutral. The assessments were done pre-dose on Day -1, Day 7, Day 14, Day 28 and Day 42. (NCT01725126)
Timeframe: Up to Day 42

,,,
InterventionpH (Mean)
Day -1Day 7Day 14Day 28Day 42
Part B-GSK2890457+Liraglutide6.255.896.075.966.08
Part B-Placebo+Liraglutide5.925.835.675.756.00
Part C-GSK2890457+Metformin5.835.425.635.635.58
Part C-Placebo+Metformin5.675.835.675.675.58

Mean Specific Gravity Values of Urine During the Double-blind Treatment Period of Part A

Urinary specific gravity is a measure of the concentration of solutes in urine. It measures the ratio of urine density compared with water density and provides information on the kidney's ability to concentrate urine. The assessments were done pre-dose at Da y 1, Day 7, Day 14, Day 28 and Day 42. (NCT01725126)
Timeframe: Up to Day 42

,
InterventionRatio (Mean)
Day 1Day 7Day 14Day 28Day 42
Part A-GSK28904571.01751.01651.01521.01221.0161
Part A-Placebo1.01931.01331.01531.01251.0155

Mean Specific Gravity Values of Urine During the Double-blind Treatment Period of Part B and C

Urinary specific gravity is a measure of the concentration of solutes in urine. It measures the ratio of urine density compared with water density and provides information on the kidney's ability to concentrate urine. The assessments were done pre-dose at Day -1, Day 7, Day 14, Day 28 and Day 42. (NCT01725126)
Timeframe: Up to Day 42

,,,
InterventionRatio (Mean)
Day -1Day 7Day 14Day 28Day 42
Part B-GSK2890457+Liraglutide1.01741.01911.01961.02391.0188
Part B-Placebo+Liraglutide1.01681.02081.02021.02321.0137
Part C-GSK2890457+Metformin1.01871.02081.02011.02131.0172
Part C-Placebo+Metformin1.01721.01971.01981.02131.0110

Number of Participants With Abnormal Urinalyisis Dipstick and Microscopic Results During the Double-blind Treatment Period of Part A

The assessments were done pre-dose at Day 1, Day 7, Day 14, Day 28 and Day 42. Only those parameters for which at least one value of abnormal urinalysis result was reported are summarized. The participants were categorized as rare, trace, +1, 2+, RBC's and WBC's as <1, 1, 2, 3 and 4. Protein concentration ranged from trace to 1+, where trace indicated lowest concentration and 1+ indicated highest concentration. Trace was the highest concentration for occult blood. Bacteria concentration ranged from rare to moderate, where rare indicated lowest concentration and moderate indicated highest concentration. Ketones ranged from trace to 1+, where trace indicated lowest concentration and 1+ indicated highest concentration. RBC and WBC ranged from <1 to 4, where <1 indicated lowest concentration and 4 indicated highest concentration. Highest concentration indicated worse outcome. (NCT01725126)
Timeframe: Up to Day 42

,
InterventionParticipants (Count of Participants)
Protein, Trace, Day 1Protein, Trace, Day 7Protein, 1+, Day 7Protein, Trace, Day 14Protein, Trace, Day 28Protein, Trace, Day 42Bacteria, Rare, Day 1Bacteria, Rare, Day 42Bacteria, Moderate, Day 42Occult blood, Trace, Day 1Occult blood, Trace, Day 14Occult blood, Trace, Day 28Ketones, 1+, Day 1Ketones, 1+, Day 7Ketones, Trace, Day 14Ketones, Trace, Day 28Ketones, Trace, Day 42RBC's, 1, Day 1RBC's, 3, Day 1RBC's, <1, Day 1RBC's, 1, Day 7RBC's, <1, Day 7RBC's, 2, Day 14RBC's, <1, Day 14RBC's, 1, Day 28RBC's, <1, Day 28RBC's, 1, Day 42RBC's, 2, Day 42RBC's, <1, Day 42WBC's, 1, Day 1WBC's, <1, Day 1WBC's, 1, Day 7WBC's, <1, Day 7WBC's, 2, Day 14WBC's, <1, Day 14WBC's, 1, Day 28WBC's, <1, Day 28WBC's, 1, Day 42WBC's, 2, Day 42WBC's, 4, Day 42
Part A-GSK28904573211420100110100010111022210121211101101
Part A-Placebo1000121011101011111000100202020001120011

Number of Participants With Abnormal Urinalyisis Dipstick and Microscopic Results During the Double-blind Treatment Period of Part B

The assessments were done pre-dose at Day -1, Day 7, Day 14, Day 28 and Day 42. Only those parameters for which at least one value of abnormal urinalysis result was reported are summarized. The participants were categorized as few, trace, +1, 2+, 3+, 0-3, 10-20, 0-5, 6-10, and 20-40. Few was the highest concentration of bacteria. Occult blood ranged from trace to 1+, trace indicated lowest and 1+ indicated highest concentration. Epithelial cell ranged from 0-5 to 10-20, 0-5 indicated lowest and 10-20 indicated highest concentration. Glucose ranged from trace to 3+, trace indicated lowest and 3+ indicated highest concentration. 0-5 was highest concentration for hyaline casts. Ketone ranged from trace to 1+, trace indicated lowest and 1+ indicated highest concentration. RBC and WBC ranged from 0-3 to 20-40, 0-3 indicated lowest and 20-40 indicated highest concentration. Highest concentration indicated worse outcome. (NCT01725126)
Timeframe: Up to Day 42

,
InterventionParticipants (Count of Participants)
Bacteria, Few, Day -1Occult Blood, 1+, Day 14Occult Blood, Trace, Day 28Occult Blood, Trace, Day 42Epithelial Cells, 10-20, Day -1Epithelial Cells, 0-5, Day 7Epithelial Cells, 6-10, Day 7Epithelial Cells, 0-5, Day 14Epithelial Cells, 0-5, Day 42Glucose, 1+, Day -1Glucose, 3+, Day -1Glucose, Trace, Day -1Glucose, 1+, Day 7Glucose, 3+, Day 7Glucose, Trace, Day 7Glucose, 1+, Day 14Glucose, 2+, Day 14Glucose, 3+, Day 14Glucose, Trace, Day 14Glucose, 1+, Day 28Glucose, 2+, Day 28Glucose, 3+, Day 28Glucose, Trace, Day 28Glucose, 1+, Day 42Glucose, 2+, Day 42Glucose, 3+, Day 42Glucose, Trace, Day 42Hyaline Casts, 0-5, Day 14Ketones, 1+, Day 7Ketones, Trace, Day 14Ketones, Trace, Day 28RBC's, 0-3, Day-1RBC's, 0-3, Day 7RBC's, 0-3, Day 14RBC's, 0-3, Day 28RBC's, 0-3, Day 42WBC's, 20-40, Day -1WBC's, 0-5, Day 7WBC's, 6-10, Day 7WBC's, 0-5, Day 14WBC's, 0-5, Day 28WBC's, 0-5, Day 42
Part B-GSK2890457+Liraglutide011101021421123111321210233011100111010111
Part B-Placebo+Liraglutide100011111002010001001002001102011000111101

Number of Participants With Abnormal Urinalyisis Dipstick and Microscopic Results During the Double-blind Treatment Period of Part C

The assessments were done pre-dose at Day -1, Day 7, Day 14, Day 28 and Day 42. The participants were categorized as few, many, moderate, trace, +1, 2+, 3+, 0-3, 10-20, 0-5, 6-10, 20-40, 40-60. Protein and ketone ranged from trace to 1+, trace indicated lowest and 1+ indicated highest concentration. Bacteria and uric acid crystals ranged from few to moderate, few indicated lowest and moderate indicated highest concentration. Trace was the highest concentration of occult blood. Epithelial cells ranged from 0-5 to >10, 0-5 indicated lowest and >10 indicated highest concentration. Glucose ranged from trace to 3+, trace indicated lowest and 3+ indicated highest concentration. 0-1 was highest concentration for hyaline casts. RBC and WBC ranged from 0-3 to 40-60, 0-3 indicated lowest and 20-40 indicated highest concentration. Highest concentration indicated worse outcome. (NCT01725126)
Timeframe: Up to Day 42

,
InterventionParticipants (Count of Participants)
Protein, 1+, Day 7Protein, Trace, Day 7Protein, Trace, Day 14Protein, 1+, Day 28Bacteria, Few, Day -1Bacteria, Many, Day -1Bacteria, Few, Day 7Bacteria, Many, Day 7Bacteria, Many, Day 14Bacteria, Moderate, Day 14Bacteria, Few, Day 28Bacteria, Many, Day 28Bacteria, Many, Day 42Bacteria, Moderate, Day 42Occult Blood, Trace, Day 42Epithelial Cells, 0-10, Day -1Epithelial Cells, 0-10, Day 7Epithelial Cells, 0-5, Day 7Epithelial Cells, 6-10, Day 7Epithelial Cells, 0-5, Day 14Epithelial Cells, >10, Day 14Epithelial Cells, 0-10, Day 28Epithelial Cells, 0-10, Day 42Glucose, 1+, Day -1Glucose, 2+, Day -1Glucose, 3+, Day -1Glucose, 1+, Day 7Glucose, 2+, Day 7Glucose, 3+, Day 7Glucose, Trace, Day 7Glucose, 1+, Day 14Glucose, 3+, Day 14Glucose, Trace, Day 14Glucose, 2+, Day 28Glucose, 3+, Day 28Glucose, Trace, Day 28Glucose, 1+, Day 42Glucose, 2+, Day 42Glucose, 3+, Day 42Glucose, Trace, Day 42Hyaline Casts, 0-1, Day 7Ketones, 1+, Day 7Ketones, Trace, Day 7Ketones, Trace, Day 14Ketones, Trace, Day 28RBC's, 0-3, Day -1RBC's, 0-3, Day 7RBC's, 0-3, Day 14RBC's, 0-3, Day 28RBC's, 0-3, Day 42Uric acid crystals, Moderate, Day 7Uric acid crystals, Few, Day 14WBC's, 0-5, Day -1WBC's, 0-5, Day 7WBC's, 6-10, Day 7WBC's, 0-5, Day 14WBC's, 0-5, Day 28WBC's, 40-60, Day 28WBC's, 6-10, Day 42
Part C-GSK2890457+Metformin12111040101001111111111116021222421221411121112211111312101
Part C-Placebo+Metformin00100101011110000000010000101110011030000001100010001101111

Number of Participants With Any Adverse Event (AE), Serious Adverse Event (SAE) or Death During Part A

An AE is defined as any untoward medical occurrence in a participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An SAE is defined as any untoward medical occurrence that, at any dose, results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, or is a congenital anomaly/birth defect, may jeopardize the participant or may require medical or surgical intervention to prevent one of the other outcomes listed in this definition, associated with liver injury and impaired liver function defined as alanine aminotransferase (ALT) >=3 x upper limit of normal (ULN), and total bilirubin >=2 x ULN or international normalized ratio >1.5. (NCT01725126)
Timeframe: Up to Follow-up (8 weeks)

,
InterventionParticipants (Count of Participants)
Any AEAny SAEAny Death
Part A-GSK28904571000
Part A-Placebo300

Number of Participants With Any AE, SAE or Death During Part B and Part C

An AE is defined as any untoward medical occurrence in a participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An SAE is defined as any untoward medical occurrence that, at any dose, results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, or is a congenital anomaly/birth defect, may jeopardize the participant or may require medical or surgical intervention to prevent one of the other outcomes listed in this definition, associated with liver injury and impaired liver function defined as ALT >=3 x ULN, and total bilirubin >=2 x ULN or international normalized ratio >1.5. (NCT01725126)
Timeframe: Up to Follow-up (8 weeks)

,,,
InterventionParticipants (Count of Participants)
Any AEAny SAEAny Death
Part B-GSK2890457+Liraglutide300
Part B-Placebo+Liraglutide100
Part C-GSK2890457+Metformin300
Part C-Placebo+Metformin300

Percent Change From Baseline in In-clinic Body Weight During the Double-blind Treatment Period of Part B and C

During the assessment of body weight in the unit, the participant wore lightweight indoor clothing and removed shoes. The assessments were done pre-dose at Day -1, Day 1, Day 7, Day 14, Day 28, Day 42 and Day 43. Baseline value was defined as the average of Day -1 and Day 1 values. Change from Baseline was calculated by subtracting the Baseline value from the individual post-Baseline (Day 7, Day 14, Day 28 and Day 42) values. Percent change was calculated by multiplying the change from Baseline value with 100. If either the Baseline or post-Baseline value was missing, the change from Baseline was set to be missing. Day 42 value was the average of Day 42 and Day 43 values. (NCT01725126)
Timeframe: Baseline (Day -1 and Day 1) up to Day 42

,,,
InterventionPercent change (Mean)
Day 7Day 14Day 28Day 42
Part B-GSK2890457+Liraglutide0.18-0.040.39-0.51
Part B-Placebo+Liraglutide-0.160.470.25-0.80
Part C-GSK2890457+Metformin0.590.600.300.50
Part C-Placebo+Metformin0.360.790.66-0.53

Time of Occurrence of Cmax (Tmax) of Liraglutide During the Double-blind Treatment Period of Part B

Blood samples were collected on Day -1 and 42 at pre-dose (0 hour), 15 minutes, 30 minutes, 1, 1.5, 2, 4 (pre-lunch), 5.5, 6, 8, 10 (pre-dinner), 11.5, 12, 14 and 24 hours post-dose. The time at which Cmax was observed was determined directly from the raw concentration-time data. (NCT01725126)
Timeframe: Day -1 and 42 at pre-dose (0 hour), 15 minutes, 30 minutes, 1, 1.5, 2, 4, 5.5, 6, 8, 10, 11.5, 12, 14 and 24 hours post-dose

,
InterventionHours (Median)
Day -1Day 42
Part B-GSK2890457+Liraglutide8.009.98
Part B-Placebo+Liraglutide9.749.92

Tmax of Metformin During the Double-blind Treatment Period of Part A

Blood samples were collected on Day 1 and 42 at pre-dose (0 hour), 15 minutes, 30 minutes, 1, 1.5, 2, 4 (pre-lunch), 5.5, 6, 8 and 10 (pre-dinner) hours post-dose. The time at which Cmax was observed was determined directly from the raw concentration-time data. (NCT01725126)
Timeframe: Day 1 and 42 at pre-dose (0 hour), 15 minutes, 30 minutes, 1, 1.5, 2, 4, 5.5, 6, 8 and 10 hours post-dose

,
InterventionHours (Median)
Day 1Day 42
Part A-GSK28904572.0002.000
Part A-Placebo3.0104.000

Body Composition -- BMI

Body mass index (BMI) measured in kg per meters squared. The analysis sample includes only participants with 24 month data who had not experienced the primary outcome by that time. (NCT00081328)
Timeframe: 24 months

Interventionkg per meters squared (Mean)
1 Metformin Alone36.7
2 Metformin + Rosliglitazone38.2
3 Metformin + Lifestyle Program35.3

Body Composition -- Bone Density

Measured by DXA, both whole body scan and AP-spine scan. The analysis sample includes only participants with 24 month data who had not experienced the primary outcome by that time. In addition, in about 1/3 of participants DXA scans could not be obtained on participants weighing more than 300 pounds (136 kg), the upper limit in size set by the machine manufacturers. Scans were considered invalid if a body part (e.g., arm, leg) was completely off or partially off the scanner, there was hand-hip overlap, or there was motion or movement during the scan. (NCT00081328)
Timeframe: 24 months

Interventiong/cm squared (Mean)
1 Metformin Alone1.15
2 Metformin + Rosliglitazone1.15
3 Metformin + Lifestyle Program1.15

Body Composition -- Fat Mass

Determined by DXA whole body scan. The analysis sample includes only participants with 24 month data who had not experienced the primary outcome by that time. In addition, in about 1/3 of participants DXA scans could not be obtained on participants weighing more than 300 pounds (136 kg), the upper limit in size set by the machine manufacturers. Scans were considered invalid if a body part (e.g., arm, leg) was completely off or partially off the scanner, there was hand-hip overlap, or there was motion or movement during the scan. (NCT00081328)
Timeframe: 24 months

Interventionkg (Mean)
1 Metformin Alone36.1
2 Metformin + Rosliglitazone39.7
3 Metformin + Lifestyle Program32.2

Body Composition -- Waist Circumference

Waist circumference (cm) measured at the iliac crest at its outermost point with the measuring tape placed around the participant in a horizontal plane parallel to the floor at the mark and the measurement teken at the end of normal expiration without the tape compressing the skin. The analysis sample includes only participants with 24 month data who had not experienced the primary outcome by that time. (NCT00081328)
Timeframe: 24 months

Interventioncm (Mean)
1 Metformin Alone110.8
2 Metformin + Rosliglitazone114.0
3 Metformin + Lifestyle Program108.6

Comorbidity -- Hypertension

A diagnosis was made by an out-of-range value >=95th percentile or systolic >=130 or diastolic >=80 sustained over 6 months or on an anti-hypertensive medication. (NCT00081328)
Timeframe: Data collected at baseline and during follow-up - 2 years to 6.5 years from randomization.

Interventionparticipants (Number)
1 Metformin Alone57
2 Metformin + Rosliglitazone53
3 Metformin + Lifestyle Program45

Comorbidity -- LDL Dyslipidemia

A diagnosis was made from out-of-range value >= 130 mg/dL sustained over 6 months or put on lipid lowering medication. (NCT00081328)
Timeframe: Data collected at baseline and during follow-up - 2 years to 6.5 years from randomization.

Interventionparticipants (Number)
1 Metformin Alone18
2 Metformin + Rosliglitazone16
3 Metformin + Lifestyle Program15

Comorbidity -- Triglycerides Dyslipidemia

A diagnosis was made by an out-of-range value >=150 mg/dL sustained over 6 months or on appropriate lipid lowering medication. (NCT00081328)
Timeframe: Data collected at baseline and during follow-up - 2 years to 6.5 years from randomization.

Interventionparticipants (Number)
1 Metformin Alone20
2 Metformin + Rosliglitazone28
3 Metformin + Lifestyle Program22

Insulin Secretion

Insulinogenic index determined from OGTT as difference in insulin at 30 minutes minus 0 minutes divided by difference in glucose at 30 minutes minus 0 minutes. The analysis sample includes only participants with 24 month data who had not experienced the primary outcome by that time. (NCT00081328)
Timeframe: 24 months

InterventionuU/mL divided by mg/dL (Median)
1 Metformin Alone.75
2 Metformin + Rosliglitazone.83
3 Metformin + Lifestyle Program.71

Insulin Sensitivity

All participants were followed to 24 months. Insulin sensitivity is measured from OGTT as inverse of fasting insulin (mL/uU). The analysis sample includes only participants with 24 month data who had not experienced the primary outcome by that time. (NCT00081328)
Timeframe: 24 months

InterventionmL/uU (Median)
1 Metformin Alone0.037
2 Metformin + Rosiglitazone0.049
3 Metformin + Lifestyle Program0.039

Number of Serious Adverse Events

Number of serious adverse events reported during the trial. Participant could have multiple episodes reported. (NCT00081328)
Timeframe: Reported as occurred during study follow-up - 2 years to 6.5 years from randomization.

Interventionepisodes of serious adverse event (Number)
1 Metformin Alone42
2 Metformin + Rosiglitazone34
3 Metformin + Lifestyle Program58

Treatment Failure (Loss of Glycemic Control)

Defined as A1c persistently >=8% over a 6-month period or persistent metabolic decompensation (inability to wean insulin within 3 months of initiation or the occurrence of a second episode within three months of discontinuing insulin) (NCT00081328)
Timeframe: Study duration - 2 years to 6.5 years of follow up from randomization

,,
Interventionparticipants (Number)
Treatment failureDid not fail treatment during trial
1 Metformin Alone120112
2 Metformin + Rosliglitazone90143
3 Metformin + Lifestyle Program109125

Change in Average 7-point SMPG Profiles From Baseline to Week 26

Participants recorded a 7-point plasma glucose profile measured before and 2 hours after each meal and at bedtime three times in a week before baseline, before visit Week 12 and before visit week 26 and the average value across the profiles performed in the week a visit for the 7-time points was calculated. Change in average 7-point SMPG was calculated by subtracting baseline value from Week 26 value. Missing data was imputed using LOCF. The on-treatment period for this efficacy variable was defined as the time from the first dose of study drug up to the day of last dose of study drug. (NCT01768559)
Timeframe: Baseline, Week 26

Interventionmmol/L (Least Squares Mean)
Lixisenatide-0.784
Insulin Glulisine QD-0.782
Insulin Glulisine TID-1.053

Change in Body Weight From Baseline to Week 26

"Primary outcome was the comparison between Lixisenatide versus Insulin Glulisine TID.~Change in body weight was calculated by subtracting baseline value from Week 26 value. Missing data was imputed using LOCF. On-treatment period for this efficacy variable was defined as the time from the first dose of study drug up to 3 days after the last dose of study drug." (NCT01768559)
Timeframe: Baseline, Week 26

Interventionkg (Least Squares Mean)
Lixisenatide-0.63
Insulin Glulisine QD1.03
Insulin Glulisine TID1.37

Change in FPG From Baseline to Week 26

Change in FPG was calculated by subtracting baseline value from Week 26 value. Missing data was imputed using LOCF. The on-treatment period for this efficacy variable was the time from the first dose of study drug up to 1 day after the last dose of study drug. (NCT01768559)
Timeframe: Baseline, Week 26

Interventionmmol/L (Least Squares Mean)
Lixisenatide-0.23
Insulin Glulisine QD-0.21
Insulin Glulisine TID-0.06

Change in Glucose Excursions From Baseline to Week 26 (in Participants Who Had an Injection of IMP Before Breakfast)

Glucose excursion = 2-hour PPG minus plasma glucose 30 minutes prior to the standardized meal test, before study drug administration. Change in glucose excursions was calculated by subtracting baseline value from Week 26 value. Missing data was imputed using LOCF. The on-treatment period for this efficacy variable was the time from the first dose of study drug up to the day of last dose of study drug. (NCT01768559)
Timeframe: Baseline, Week 26

Interventionmmol/L (Mean)
Lixisenatide-3.42
Insulin Glulisine QD-1.59
Insulin Glulisine TID-1.56

Change in HbA1c From Baseline to Week 26

Change in HbA1C was calculated by subtracting baseline value from Week 26 value. Missing data was imputed using last on-treatment observation carried forward (LOCF). On-treatment period for this efficacy variable was defined as the time from the first dose of study drug up to 14 days after the last dose of study drug. Here, number of participants analyzed = participants with baseline and at least one post-baseline HbA1c assessment during on-treatment period. (NCT01768559)
Timeframe: Baseline, Week 26

Interventionpercentage of hemoglobin (Least Squares Mean)
Lixisenatide-0.63
Insulin Glulisine QD-0.58
Insulin Glulisine TID-0.84

Change in Insulin Glargine Dose From Baseline to Week 26

Change in Insulin glargine dose was calculated by subtracting the baseline value from Week 26 value. Missing data was imputed using LOCF. The on-treatment period for this efficacy variable was the time from the first dose of study drug up to the day of last dose of study drug. (NCT01768559)
Timeframe: Baseline, Week 26

InterventionU (Least Squares Mean)
Lixisenatide0.7
Insulin Glulisine QD-0.06
Insulin Glulisine TID-3.13

Change in PPG From Baseline to Week 26 (in Participants Who Had an Injection of Investigational Medicinal Product [IMP] Before Breakfast)

The 2-hour PPG test measured blood glucose 2 hours after eating a standardized meal. Change in PPG was calculated by subtracting baseline value from Week 26 value. Missing data was imputed using LOCF. The on-treatment period for this efficacy variable was the time from the first dose of study drug up to the day of last dose of study drug. (NCT01768559)
Timeframe: Baseline, Week 26

Interventionmmol/L (Mean)
Lixisenatide-3.93
Insulin Glulisine QD-1.62
Insulin Glulisine TID-1.87

Insulin Glulisine Dose at Week 26

The on-treatment period for this efficacy variable was the time from the first dose of study drug up to the day of last dose of study drug. Missing data was imputed using LOCF. (NCT01768559)
Timeframe: Week 26

InterventionU (Mean)
Insulin Glulisine QD9.97
Insulin Glulisine TID20.24

Percentage of Participants Who Reached the Target of HbA1c <7% and Had no Weight Gain at Week 26

The on-treatment period for HbA1c assessment was defined as the time from the first dose of study drug up to 14 days after the last dose of study drug. The on-treatment period for body weight assessment was defined as the time from the first dose of study drug up to 3 days after the last dose of study drug. (NCT01768559)
Timeframe: Week 26

Interventionpercentage of participants (Number)
Lixisenatide31.2
Insulin Glulisine QD16.7
Insulin Glulisine TID17.6

Percentage of Participants Who Reached the Target of HbA1c <7% at Week 26 and Did Not Experienced Documented (Plasma Glucose <60 mg/dL) Symptomatic Hypoglycemia During 26 Week Treatment Period

The on-treatment period for HbA1c assessment was defined as the time from the first dose of study drug up to 14 days after the last dose of study drug. The on-treatment period for symptomatic hypoglycemia assessment was defined as the time from the first dose of study drug up to 1 day after the last dose of study drug. (NCT01768559)
Timeframe: Week 26

Interventionpercentage of participants (Number)
Lixisenatide29.4
Insulin Glulisine QD24.2
Insulin Glulisine TID26.1

Percentage of Participants Who Reached the Target of HbA1c <7%, Had no Weight Gain at Week 26, and Did Not Experience Documented (Plasma Glucose <60 mg/dL) Symptomatic Hypoglycemia During 26-Week Treatment Period

The on-treatment period for HbA1c assessment was defined as the time from the first dose of study drug up to 14 days after the last dose of study drug. The on-treatment period for body weight assessment was defined as the time from the first dose of study drug up to 3 days after the last dose of study drug. The on-treatment period for symptomatic hypoglycemia assessment was defined as the time from the first dose of study drug up to 1 day after the last dose of study drug. Participants without post-baseline on-treatment values (HbA1c and body weight) that were no more than 30 days apart were counted as non-responders if at least one of the components (HbA1c and/or body weight) was available and showed non-response, or if they experienced at least one documented symptomatic hypoglycemia during the on-treatment period. Otherwise, they were counted as missing data. (NCT01768559)
Timeframe: Week 26

Interventionpercentage of participants (Number)
Lixisenatide22.2
Insulin Glulisine QD9.2
Insulin Glulisine TID10.8

Percentage of Participants With no Weight Gain at Week 26

The on-treatment period for this efficacy variable was the time from the first dose of study drug up to 3 days after the last dose of study drug. (NCT01768559)
Timeframe: Week 26

Interventionpercentage of participants (Number)
Lixisenatide64.7
Insulin Glulisine QD36.6
Insulin Glulisine TID30.5

Total Insulin Dose at Week 26

"The on-treatment period for this efficacy variable was the time from the first dose of study drug up to the day of last dose of study drug. Missing data was imputed using LOCF.~The outcome is reporting results of total insulin (amounts of Insulin Glargine plus Insulin Glulisine ) only for the arms in which Insulin Glulisine was administered and is not applicable for the lixisenatide arm in which only Insulin Glargine is administered. Change in dose of the insulin used by patients in the Lixisenatide arm (i.e. Insulin Glargine) is reported in the secondary Outcome Measure 9." (NCT01768559)
Timeframe: Week 26

InterventionU (Mean)
Insulin Glulisine QD73.61
Insulin Glulisine TID81.05

Percentage of Participants With Documented Symptomatic and Severe Symptomatic Hypoglycemia

Documented symptomatic hypoglycemia was an event during which typical symptoms of hypoglycemia were accompanied by a measured plasma glucose concentration of <60 mg/dL (3.3 mmol/L). Severe symptomatic hypoglycemia was symptomatic hypoglycemia event in which the participant required the assistance of another person and was associated with either a plasma glucose level below 36 mg/dL (2.0 mmol/L) or prompt recovery after oral carbohydrate, intravenous glucose, or glucagon administration, if no plasma glucose measurement was available. (NCT01768559)
Timeframe: First dose of study drug up to 3 days after the last dose administration (maximum of 185 days)

,,
Interventionpercentage of participants (Number)
Documented symptomatic hypoglycemiaSevere symptomatic hypoglycemia
Insulin Glulisine QD37.50.7
Insulin Glulisine TID44.60
Lixisenatide31.50

Percentage of Participants With HbA1c Level <7% and ≤6.5% at Week 26

The on-treatment period for this efficacy variable was defined as the time from the first dose of study drug up to 14 days after the last dose of study drug. Missing data was imputed using LOCF. (NCT01768559)
Timeframe: Week 26

,,
Interventionpercentage of participants (Number)
HbA1c ≤6.5%HbA1c <7.0%
Insulin Glulisine QD17.838.4
Insulin Glulisine TID30.849.2
Lixisenatide20.542.1

Change From Baseline in Body Weight at Week 30

Change in body weight following 30 weeks of therapy (i.e., body weight at Week 30 minus body weight at baseline) (NCT00993187)
Timeframe: Baseline and Week 30

Interventionkg (Least Squares Mean)
Sitagliptin/Metformin-0.83
Glimepiride0.90

Change From Baseline in Fasting Plasma Glucose (FPG) at Week 30

Blood glucose was measured on a fasting basis (collected after an 8- to 10-hour fast). FPG is expressed as mg/dL. Blood was drawn at predose on Day 1 and after 30 weeks of treatment to determine change in plasma glucose levels (i.e., FPG at Week 30 minus FPG at baseline). (NCT00993187)
Timeframe: Baseline and Week 30

Interventionmg/dL (Least Squares Mean)
Sitagliptin/Metformin-47.0
Glimepiride-23.5

Change From Baseline in Hemoglobin A1C (HbA1C) at Week 30

HbA1C is blood marker used to report average blood glucose levels over a prolonged periods of time and is reported as a percentage (%). Change in A1C following 30 weeks of therapy (i.e., A1C at Week 30 minus A1C at baseline). (NCT00993187)
Timeframe: Baseline and Week 30

InterventionPercent of total hemoglobin (Least Squares Mean)
Sitagliptin/Metformin-1.5
Glimepiride-0.7

Number of Participants Who Discontinued Study Drug Due to an Adverse Event

An AE is any unfavorable and unintended change in the structure, function or chemistry of the body temporally associated with study drug administration whether or not considered related to the use of the product. (NCT00993187)
Timeframe: Up to 30 weeks

InterventionParticipants (Number)
Sitagliptin/Metformin8
Glimepiride8

Number of Participants Who Experienced at Least One Adverse Event (AE)

An adverse event (AE) is any unfavorable and unintended change in the structure, function or chemistry of the body temporally associated with study drug administration whether or not considered related to the use of the product. (NCT00993187)
Timeframe: Up to 32 weeks

InterventionParticipants (Number)
Sitagliptin/Metformin88
Glimepiride101

Percentage of Participants With HbA1C < 7.0% at Week 30

HbA1C is blood marker used to report average blood glucose levels over a prolonged periods of time and is reported as a percentage (%). (NCT00993187)
Timeframe: Week 30

InterventionPercentage of Participants (Number)
Sitagliptin/Metformin81.2
Glimepiride40.1

Percentage of Participants With One or More Episodes of Hypoglycemia

Symptomatic episodes assessed as likely to be due to hypoglycemia were reported by investigators as adverse experiences of hypoglycemia. Adverse experiences of hypoglycemia were based on all reports of hypoglycemia; a concurrent glucose measurement was not required. (NCT00993187)
Timeframe: Up to Week 30

InterventionPercentage of participants (Number)
Sitagliptin/Metformin5.5
Glimepiride20.1

Average Daily Insulin Glargine Dose at Week 24

Missing data was imputed using LOCF. On-treatment period for this efficacy variable was defined as the time from the first dose of study drug till before the introduction of rescue medication and up to the date of last injection of IMP. (NCT01476475)
Timeframe: Week 24

InterventionUnits (U) (Least Squares Mean)
Insulin Glargine/Lixisenatide Fixed Ratio Combination36.08
Insulin Glargine39.32

Change in 2-hour Plasma Glucose Excursion From Baseline to Week 24

2-hour plasma glucose excursion = 2-hour PPG minus plasma glucose value obtained 30 minutes prior to the start of the meal and before IMP administration. Change in plasma glucose excursion was calculated by subtracting baseline value from Week 24 value. Missing data was imputed using LOCF. On-treatment period for this efficacy variable was defined as the time from the first dose of study drug till before the introduction of rescue medication and up to the date of last injection of IMP. (NCT01476475)
Timeframe: Baseline, Week 24

Interventionmmol/L (Least Squares Mean)
Insulin Glargine/Lixisenatide Fixed Ratio Combination-3.91
Insulin Glargine-0.67

Change in 2-hour Postprandial Plasma Glucose (PPG) From Baseline to Week 24

The 2-hour PPG test measured blood glucose 2 hours after eating a standardized meal. Change in PPG was calculated by subtracting baseline value from Week 24 value. Missing data was imputed using LOCF. On-treatment period for this efficacy variable was defined as the time from the first dose of study drug till before the introduction of rescue medication and up to the date of last injection of IMP. (NCT01476475)
Timeframe: Baseline, Week 24

Interventionmmol/L (Least Squares Mean)
Insulin Glargine/Lixisenatide Fixed Ratio Combination-7.49
Insulin Glargine-4.33

Change in Average 7-Point Self-Monitored Plasma Glucose (SMPG) Profiles From Baseline to Week 24

Participants recorded a 7-point plasma glucose profile measured before and 2-hours after each meal and at bedtime, over a single day, once in a week before baseline, before visit Week 12 and before visit Week 24 and the average value across the profiles performed in the week before a visit for the 7-time points was calculated. Change in average 7-point SMPG was calculated by subtracting baseline value from Week 24 value. Missing data was imputed using LOCF. On-treatment period for this efficacy variable was defined as the time from the first dose of study drug till before the introduction of rescue medication and up to the date of last injection of IMP. (NCT01476475)
Timeframe: Baseline, Week 24

Interventionmmol/L (Least Squares Mean)
Insulin Glargine/Lixisenatide Fixed Ratio Combination-3.23
Insulin Glargine-2.93

Change in Body Weight From Baseline to Week 24

Change in body weight was calculated by subtracting baseline value from Week 24 value. Missing data was imputed using LOCF. On-treatment period for this efficacy variable was defined as the time from the first dose of study drug till before the introduction of rescue medication and up to 3 days after the last injection of IMP. (NCT01476475)
Timeframe: Baseline, Week 24

Interventionkg (Least Squares Mean)
Insulin Glargine/Lixisenatide Fixed Ratio Combination-0.97
Insulin Glargine0.48

Change in FPG From Baseline to Week 24

Change in FPG was calculated by subtracting baseline value from Week 24 value. Missing data was imputed using LOCF. On-treatment period for this efficacy variable was defined as the time from the first dose of study drug till before the introduction of rescue medication and up to 1 day after the last injection of IMP. (NCT01476475)
Timeframe: Baseline, Week 24

Interventionmmol/L (Least Squares Mean)
Insulin Glargine/Lixisenatide Fixed Ratio Combination-3.35
Insulin Glargine-3.51

Change in HbA1c From Baseline to Week 24

Change in HbA1c was calculated by subtracting baseline value from Week 24 value. Missing data was imputed using last observation carried forward (LOCF). On-treatment period for this efficacy variable was defined as the time from the first dose of study drug till before the introduction of rescue medication and up to 14 days after the last injection of investigational medicinal product (IMP). (NCT01476475)
Timeframe: Baseline, Week 24

Interventionpercentage of hemoglobin (Least Squares Mean)
Insulin Glargine/Lixisenatide Fixed Ratio Combination-1.82
Insulin Glargine-1.64

Percentage of Participants Reaching HbA1c <7% at Week 24 With no Documented Symptomatic Hypoglycemia During 24-week Treatment Period

Documented symptomatic hypoglycemia was an event during which typical symptoms of hypoglycemia were accompanied by a measured plasma glucose concentration of ≤70 mg/dL (3.9 mmol/L). Participants without any post-baseline on-treatment value for HbA1c were counted as non-responders if they experienced at least one documented symptomatic hypoglycemia before the introduction of rescue medication and up to 1 day after the last injection of IMP. Otherwise, they were counted as missing data. On-treatment period for this efficacy variable was defined as the time from the first dose of study drug till before the introduction of rescue medication and up to 14 days after the last injection of IMP. (NCT01476475)
Timeframe: Baseline up to Week 24

Interventionpercentage of participants (Number)
Insulin Glargine/Lixisenatide Fixed Ratio Combination67.5
Insulin Glargine59.0

Percentage of Participants Reaching HbA1c <7% With no Body Weight Gain at Week 24

Participants without any post-baseline on-treatment values (for HbA1c and body weight) that were no more than 30 days apart were counted as non-responders if at least one of the components (for HbA1c and body weight) was available and showed non-response. Otherwise, they were counted as missing data. (NCT01476475)
Timeframe: Week 24

Interventionpercentage of participants (Number)
Insulin Glargine/Lixisenatide Fixed Ratio Combination56.3
Insulin Glargine37.3

Percentage of Participants Requiring Rescue Therapy During 24-week Treatment Period

Routine fasting SMPG and central laboratory FPG (and HbA1c after Week 12) values were used to determine the requirement of rescue medication. If fasting SMPG value exceed the specified limit for 3 consecutive days, the central laboratory FPG (and HbA1c after Week 12) were performed. Threshold values from Week 8 to Week 12: fasting SMPG/FPG >240 mg/dL (13.3 mmol/L), and from Week 12 to Week 30: fasting SMPG/FPG >200 mg/dL (11.1 mmol/L) or HbA1c >8%. (NCT01476475)
Timeframe: Baseline up to Week 24

Interventionpercentage of participants (Number)
Insulin Glargine/Lixisenatide Fixed Ratio Combination0
Insulin Glargine0.6

Change in 30 Minute and 1-hour Plasma Glucose Excursion From Baseline to Week 24

30-minute and 1-hour plasma glucose excursion = 30-minute and 1-hour PPG minus plasma glucose value obtained 30 minutes prior to the start of the meal and before IMP administration. Change in plasma glucose excursion was calculated by subtracting baseline value from Week 24 value. Missing data was imputed using LOCF. On-treatment period for this efficacy variable was defined as the time from the first dose of study drug till before the introduction of rescue medication and up to the date of last injection of IMP. (NCT01476475)
Timeframe: Baseline, Week 24

,
Interventionmmol/L (Least Squares Mean)
30-minute plasma glucose excursion (n=151, 152)1-hour plasma glucose excursion (n=150, 152)
Insulin Glargine-0.05-0.44
Insulin Glargine/Lixisenatide Fixed Ratio Combination-1.47-2.34

Change in 30-minute and 1-hour PPG From Baseline to Week 24

The 30 minute and 1-hour PPG test measured blood glucose 30 minutes and 1-hour after eating a standardized meal. Change in PPG was calculated by subtracting baseline value from Week 24 value. Missing data was imputed using LOCF. On-treatment period for this efficacy variable was defined as the time from the first dose of study drug till before the introduction of rescue medication and up to the date of last injection of IMP. (NCT01476475)
Timeframe: Baseline, Week 24

,
Interventionmmol/L (Least Squares Mean)
30-minute PPG (n=151, 153)1-hour PPG (n=150, 153)
Insulin Glargine-3.76-4.10
Insulin Glargine/Lixisenatide Fixed Ratio Combination-5.01-5.94

Percentage of Participants With Documented Symptomatic and Severe Symptomatic Hypoglycemia

Documented symptomatic hypoglycemia was an event during which typical symptoms of hypoglycemia were accompanied by a measured plasma glucose concentration of ≤70 mg/dL (3.9 mmol/L).Severe symptomatic hypoglycemia was an event requiring assistance of another person to actively administer carbohydrate, glucagon, or other resuscitative actions. These episodes were associated with sufficient neuroglycopenia to induce seizure, unconsciousness or coma. All episodes in which neurological impairment was severe enough to prevent self-treatment and which were thought to place participants at risk for injury to themselves or others. (NCT01476475)
Timeframe: First dose of study drug up to 3 days after the last dose administration (maximum of 219 days)

,
Interventionpercentage of participants (Number)
Documented symptomatic hypoglycemiaSevere Symptomatic Hypoglycemia
Insulin Glargine (Lantus® SoloSTAR®)22.80.0
Insulin Glargine/Lixisenatide Fixed Ratio Combination21.70.0

Percentage of Participants With HbA1c ≤6.5 % or <7.0 % at Week 24

On-treatment period for this efficacy variable was defined as the time from the first dose of study drug till before the introduction of rescue medication and up to 14 days after the last injection of IMP. (NCT01476475)
Timeframe: Week 24

,
Interventionpercentage of participants (Number)
HbA1c ≤6.5%HbA1c <7.0%
Insulin Glargine64.678.3
Insulin Glargine/Lixisenatide Fixed Ratio Combination71.984.4

Change in Body Weight From Baseline

Change from baseline in body weight after 26 weeks of treatment. (NCT01973231)
Timeframe: Week 0, week 26

Interventionkg (Mean)
Liraglutide-4.24
Lixisenatide-3.69

Change in Fasting Plasma Glucose (FPG) From Baseline

Change from baseline in FPG after 26 weeks of treatment. (NCT01973231)
Timeframe: Week 0, week 26

Interventionmmol/L (Mean)
Liraglutide-2.904
Lixisenatide-1.644

Change in Glycosylated Haemoglobin (HbA1c) From Baseline

Change from baseline in HbA1c after 26 weeks of treatment. (NCT01973231)
Timeframe: Week 0, week 26

InterventionPercent (%) glycosylated haemoglobin (Mean)
Liraglutide-1.809
Lixisenatide-1.238

Number of Treatment Emergent Adverse Events (TEAEs)

A Treatment Emergent Adverse Event (TEAE) was defined as an event that had onset date on or after the first day of exposure to randomised treatment and no later than 7 days after the last day of randomised treatment. Severity was assessed by investigator. (NCT01973231)
Timeframe: Weeks 0-26

,
Interventionevents (Number)
EventsSeriousSevereModerateMild
Liraglutide5401310109421
Lixisenatide4357384348

Subjects Who Achieve HbA1c Below 7.0% (53 mmol/Mol) (American Diabetes Association (ADA) Target) (Yes/no)

Subjects who achieved HbA1c below 7.0% (53 mmol/mol) after 26 weeks of treatment (yes/no). (NCT01973231)
Timeframe: After 26 weeks of treatment

,
Interventionpercentage (%) of subjects (Number)
YesNo
Liraglutide74.225.8
Lixisenatide45.554.5

Subjects Who Achieve HbA1c Below 7.0% (53 mmol/Mol) and no Weight Gain (Yes/no)

Subjects who achieved HbA1c below 7.0% (53 mmol/mol) and no weight gain after 26 weeks of treatment (yes/no). (NCT01973231)
Timeframe: After 26 weeks of treatment

,
Interventionpercentage (%) of subjects (Number)
YesNo
Liraglutide66.533.5
Lixisenatide41.958.1

Subjects Who Achieve HbA1c Equal to or Below 6.5% (48 mmol/Mol) (American Association of Clinical Endocrinologists [AACE] Target) (Yes/no)

Subjects who achieved HbA1c below equal to or below 6.5% (48 mmol/mol) after 26 weeks of treatment (yes/no). (NCT01973231)
Timeframe: After 26 weeks of treatment

,
Interventionpercentage (%) of subjects (Number)
YesNo
Liraglutide54.645.4
Lixisenatide26.273.8

Change in Body Weight

Change from baseline in body weight was analysed after 26 weeks of treatment. Analysis population set: FAS: all randomised subjects receiving at least one dose of any of the trial products. Missing values were imputed using MMRM. (NCT01907854)
Timeframe: From baseline to week 26

Interventionkg (Mean)
Liraglutide-3.32
Sitagliptin-1.80

Change in Fasting Plasma Glucose

Change from baseline in fasting plasma glucose was analysed after 26 weeks of treatment. Missing values were imputed using MMRM. (NCT01907854)
Timeframe: From baseline to week 26

Interventionnmol/L (Mean)
Liraglutide-1.967
Sitagliptin-0.588

Change in HbA1c (Glycosylated Haemoglobin)

Change from baseline in HbA1c was analysed after 26 weeks of treatment. Analysis population set: full analysis set (FAS); all randomised subjects receiving at least one dose of any of the trial products. Missing values were imputed using mixed model for repeated measurements (MMRM). (NCT01907854)
Timeframe: From baseline to week 26

Interventionpercentage of glycosylated haemoglobin (Mean)
Liraglutide-1.146
Sitagliptin-0.529

Number of Treatment Emergent Adverse Events (TEAEs)

A treatment emergent adverse event (TEAE) was defined as an event that had an onset date (or increase in severity) on or after the first day of exposure to randomised treatment and no later than seven days after the last day of randomised treatment. The number of TEAEs was recorded during 26 weeks of treatment plus one week follow-up period. (NCT01907854)
Timeframe: During 26 weeks of treatment plus one week follow-up period.

Interventionnumber of events (Number)
Liraglutide455
Sitagliptin318

Change in Fasting Blood Lipids

Ratio to baseline in fasting blood lipids (total cholesterol, low density lipoprotein [LDL], very low density lipoprotein [VLDL], high density lipoprotein [HDL], triglycerides, and free fatty acids) were analysed after 26 weeks treatment. Missing values were imputed using MMRM. Here we are presenting ratio to baseline data. (NCT01907854)
Timeframe: From baseline to week 26

,
Interventionratio (Mean)
Total cholesterolLDL cholesterolVLDL cholesterolHDL cholesterolTriglyceridesFree Fatty acids
Liraglutide1.0111.0491.0621.0041.0891.086
Sitagliptin1.0451.1211.0750.9971.0991.104

Change in Systolic Blood Pressure and Diastolic Blood Pressure

Change from baseline in systolic and diastolic blood pressure were analysed after 26 weeks of treatment. Missing values were imputed using MMRM. (NCT01907854)
Timeframe: From baseline to week 26

,
InterventionmmHg (Mean)
Systolic Blood PressureDiastolic Blood Pressure
Liraglutide-3.6-0.23
Sitagliptin-2.57-0.81

Subjects Who Achieve HbA1c Below 7.0% (53 mmol/Mol) (American Diabetes Association Target) (y/n)

Number of subjects who achieve HbA1c <7.0% were analysed after 26 weeks of treatment. Missing values were imputed using MMRM. (NCT01907854)
Timeframe: After 26 weeks of treatment

,
Interventionpercentage (%) (Number)
YesNo
Liraglutide50.649.4
Sitagliptin26.973.1

Change in Breast Density at 12 Months

Change in dense breast volume at 12 months (NCT02028221)
Timeframe: Baseline, 12 months

Interventioncm^3 (Mean)
Placebo-12.11
Metformin-14.75

Change in Breast Density at 6 Months

change of dense breast volume at 6 months (NCT02028221)
Timeframe: baseline, 6 months

Interventioncm^3 (Mean)
Placebo-5.45
Metformin-13.71

Change From Baseline in Body Weight at 6 and 12 Months

(NCT02028221)
Timeframe: baseline, 6 months, 12 months

,
Interventionkg (Mean)
Baseline6 months12 months
Metformin101.599.699.3
Placebo102.3102.1103.2

Change From Baseline in Serum IGF-1 to IGFBP-3 Ratio at 6 and 12 Months

(NCT02028221)
Timeframe: baseline, 6 months, 12 months

,
Interventiondata presented as ratio; no unit (Mean)
Baseline6 months12 months
Metformin0.1700.1690.165
Placebo0.1780.1780.171

Change From Baseline in Serum Insulin Levels at 6 and 12 Months

(NCT02028221)
Timeframe: baseline, 6 months, 12 months

,
InterventionuIU/ml (Mean)
Baseline6 months12 months
Metformin13.511.911.7
Placebo14.614.013.1

Change From Baseline in Serum Leptin to Adiponectin Ratio at 6 and 12 Months

(NCT02028221)
Timeframe: baseline, 6 months, 12 months

,
Interventiondata presented as ratio; no unit (Mean)
Baseline6 months12 months
Metformin0.0280.0250.026
Placebo0.0230.0220.021

Change From Baseline in Waist Circumference at 6 and 12 Months

(NCT02028221)
Timeframe: baseline, 6 months, 12 months

,
Interventioncm (Mean)
Baseline6 months12 months
Metformin111.2108.9108.3
Placebo110.3111.6111.8

Area Under the Concentration-time Curve of Empa in Plasma (AUCτ,ss)

Area under the concentration-time curve of Empa in plasma at steady state over a uniform dosing interval τ (AUCτ,ss). (NCT01276288)
Timeframe: Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 16, and 24 post-dose on Day 5 with EMPA alone and on Day 9 with EMPA plus diuretic. The Pre-dose values were averaged over Days 1 to 4 with EMPA alone and on Days 7 & 8 with EMPA plus diuretic

Interventionnmol*h/L (Geometric Mean)
Empagliflozin (Empa)4990
Empa+ HCT5570
Empa + TOR5260

Area Under the Concentration-time Curve of HCT in Plasma (AUCτ,ss)

Area under the concentration-time curve of HCT in plasma at steady state over a uniform dosing interval τ (AUCτ,ss). (NCT01276288)
Timeframe: Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 16, and 24 post-dose on Day 4 with HCT alone and on Day 9 with EMPA plus HCT. The Pre-dose values were averaged over Days 1 to 3 with HCT alone and on Days 7 & 8 with EMPA plus HCT

Interventionng*h/mL (Geometric Mean)
Hydrochlorothiazide (HCT)1040
HCT+ Empa1000

Area Under the Concentration-time Curve of TOR in Plasma (AUCτ,ss)

Area under the concentration-time curve of TOR in plasma at steady state over a uniform dosing interval τ (AUCτ,ss). (NCT01276288)
Timeframe: Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 16, and 24 post-dose on Day 4 with TOR alone and on Day 9 with EMPA plus TOR. The Pre-dose values were averaged over Days 1 to 3 with TOR alone and on Days 7 & 8 with EMPA plus TOR

Interventionng*h/mL (Geometric Mean)
Torasemide (TOR)1320
TOR+ Empa1340
TOR Metabolite (TOR-M1)74.8
TOR Metabolite (TOR-M3)40.5
TOR-M1+ Empa78.1
TOR-M3 + Empa41.8

Change in Body Weight From Baseline

"Change in body weight from baseline , where baseline was defined as the last measurement before trial drug administration of each treatment period~The mean change from baseline was evaluated as:~Empa: day 6- baseline, HCT: day 5-baseline, TOR: day 5-baseline, Empa+ HCT: day 10- baseline, Empa+ TOR: day 10- baseline,~The mean for the Empa arm represent combined adjusted means of all four sequences that is Empa administered before or after the administration of either TOR, HCT and their combination with Empa" (NCT01276288)
Timeframe: baseline and then day 6 for Empa, day 5 for TOR and HCT, day 10 for Empa+TOR and Empa+HCT

Interventionkg (Mean)
Empagliflozin (Empa)-1.365
Hydrochlorothiazide (HCT)-1.040
Torasemide (TOR)-0.380
Empa+ HCT-2.030
Empa + TOR-1.750

Change in pH in Capillary or Arterialised Blood From Baseline

"Change in pH in capillary or arterialised blood from baseline, where baseline was defined as the last measurement before trial drug administration of each treatment period~The mean change from baseline was evaluated as:~Empa: day 6- baseline, HCT: day 5-baseline, TOR: day 5-baseline, Empa+ HCT: day 10- baseline, Empa+ TOR: day 10- baseline,~The mean for the Empa arm represent combined adjusted means of all four sequences that is Empa administered before or after the administration of either TOR, HCT and their combination with Empa" (NCT01276288)
Timeframe: baseline and then day 6 for Empa, day 5 for TOR and HCT, day 10 for Empa+TOR and Empa+HCT

InterventionpH (Mean)
Empagliflozin (Empa)-0.006
Hydrochlorothiazide (HCT)0.003
Torasemide (TOR)-0.002
Empa+ HCT0.008
Empa + TOR-0.005

Change in Serum Concentration of Aldosterone From Baseline

"Change in serum concentration of Aldosterone from baseline , where baseline was defined as the measurement obtained before first drug administration in the first period~The mean change from baseline was evaluated as:~Empa: day 6- baseline, HCT: day 5-baseline, TOR: day 5-baseline, Empa+ HCT: day 10- baseline, Empa+ TOR: day 10- baseline,~The mean for the Empa arm represent combined adjusted means of all four sequences that is Empa administered before or after the administration of either TOR, HCT and their combination with Empa" (NCT01276288)
Timeframe: baseline and then day 6 for Empa, day 5 for TOR and HCT, day 10 for Empa+TOR and Empa+HCT

Interventionnmol/L (Mean)
Empagliflozin (Empa)-0.018
Hydrochlorothiazide (HCT)0.099
Torasemide (TOR)0.023
Empa+ HCT0.124
Empa + TOR0.123

Change in Serum Concentration of Alkaline Phosphatase (ALP) From Baseline

"Change in serum concentration of ALP from baseline, where baseline was defined as the measurement obtained before first drug administration in the first period~The mean change from baseline was evaluated as:~Empa: day 6- baseline, HCT: day 5-baseline, TOR: day 5-baseline, Empa+ HCT: day 10- baseline, Empa+ TOR: day 10- baseline,~The mean for the Empa arm represent combined adjusted means of all four sequences that is Empa administered before or after the administration of either TOR, HCT and their combination with Empa" (NCT01276288)
Timeframe: baseline and then day 6 for Empa, day 5 for TOR and HCT, day 10 for Empa+TOR and Empa+HCT

InterventionU/L (Mean)
Empagliflozin (Empa)2.750
Hydrochlorothiazide (HCT)3.000
Torasemide (TOR)2.400
Empa+ HCT6.500
Empa + TOR5.800

Change in Serum Concentration of Fibroblast Growth Factor-23 (FGF- 23) From Baseline

"Change in serum concentration of fibroblast growth factor-23 (FGF- 23) from baseline, where baseline was defined as the measurement obtained before first drug administration in the first period~The mean change from baseline was evaluated as:~Empa: day 6- baseline, HCT: day 5-baseline, TOR: day 5-baseline, Empa+ HCT: day 10- baseline, Empa+ TOR: day 10- baseline, The mean for the Empa arm represent combined adjusted means of all four sequences that is Empa administered before or after the administration of either TOR, HCT and their combination with Empa" (NCT01276288)
Timeframe: baseline and then day 6 for Empa, day 5 for TOR and HCT, day 10 for Empa+TOR and Empa+HCT

InterventionRU/mL (Mean)
Empagliflozin (Empa)50.305
Hydrochlorothiazide (HCT)29.050
Torasemide (TOR)-0.680
Empa+ HCT109.860
Empa + TOR13.820

Change in Serum Osmolality From Baseline

"Changes in serum osmolality from baseline based on a blood sample.~Baseline was defined as the measurement obtained before the first drug administration in the first period.~The mean change from baseline was evaluated as:~Empa: day 6- baseline, HCT: day 5-baseline, TOR: day 5-baseline, Empa+ HCT: day 10- baseline, Empa+ TOR: day 10- baseline,~The mean for the Empa arm represent combined adjusted means of all four sequences that is Empa administered before or after the administration of either TOR, HCT and their combination with Empa" (NCT01276288)
Timeframe: baseline and then day 6 for Empa, day 5 for TOR and HCT, day 10 for Empa+TOR and Empa+HCT

InterventionmOsm/Kg (Mean)
Empagliflozin (Empa)3.950
Hydrochlorothiazide (HCT)-7.500
Torasemide (TOR)-5.500
Empa+ HCT-2.200
Empa + TOR10.500

Change in Urea Concentration in Urine

"Change in urea concentration in urine from baseline, where baseline was defined as the measurement obtained before first drug administration in the first period~The mean change from baseline was evaluated as:~Empa: day 6- baseline, HCT: day 5-baseline, TOR: day 5-baseline, Empa+ HCT: day 10- baseline, Empa+ TOR: day 10- baseline,~The mean for the Empa arm represent combined adjusted means of all four sequences that is Empa administered before or after the administration of either TOR, HCT and their combination with Empa" (NCT01276288)
Timeframe: baseline and then day 6 for Empa, day 5 for TOR and HCT, day 10 for Empa+TOR and Empa+HCT

Interventionmmol/L (Mean)
Empagliflozin (Empa)-1.515
Hydrochlorothiazide (HCT)67.570
Torasemide (TOR)35.710
Empa+ HCT11.780
Empa + TOR48.690

Change in Urinary Excretion in a 24-hour Period of N-terminal Telopeptide (NTx) From Baseline

"Change in urinary excretion in a 24-hour period of N-terminal telopeptide (NTx) from baseline, where baseline was defined as the value obtained from the last 24-hour (h) collection period before the first drug administration in the first treatment period.~The mean change from baseline was evaluated as:~Empa: day 5- baseline, HCT: day 4-baseline, TOR: day 4-baseline, Empa+ HCT: day 9- baseline, Empa+ TOR: day 9- baseline,~The means for the Empa arm represent combined adjusted means of all four sequences that is Empa administered before or after the administration of either TOR, HCT and their combination with Empa" (NCT01276288)
Timeframe: 24 hour sampling interval at baseline and then day 5 for Empa, day 4 for TOR and HCT, day 9 for Empa+TOR and Empa+HCT

InterventionnM BCE/ mMC (Mean)
Empagliflozin (Empa)6.010
Hydrochlorothiazide (HCT)0.730
Torasemide (TOR)2.030
Empa+ HCT1.380
Empa + TOR3.900

Change in Urinary Weight From Baseline

"Change from baseline in urinary weight in a 24 hour (h)- collection period, where baseline is the last 24-h collection period before first trial drug administration in each treatment period.~The mean change from baseline was evaluated as:~Empa: day 5- baseline, HCT: day 4-baseline, TOR: day 4-baseline, Empa+ HCT: day 9- baseline, Empa+ TOR: day 9- baseline,~The mean for the Empa arm represent combined adjusted means of all four sequences that is Empa administered before or after the administration of either TOR, HCT and their combination with Empa" (NCT01276288)
Timeframe: 24 hour sampling interval at baseline and then day 5 for Empa, day 4 for TOR and HCT, day 9 for Empa+TOR and Empa+HCT

Interventiong/day (Mean)
Empagliflozin (Empa)134.700
Hydrochlorothiazide (HCT)-55.300
Torasemide (TOR)-39.000
Empa+ HCT429.000
Empa + TOR353.200

Change in Urine Osmolality From Baseline

"Change in urine osmolality from baseline, where baseline was defined as the measurement obtained before first drug administration in the first period~The mean change from baseline was evaluated as:~Empa: day 6- baseline, HCT: day 5-baseline, TOR: day 5-baseline, Empa+ HCT: day 10- baseline, Empa+ TOR: day 10- baseline,~The mean for the Empa arm represent combined adjusted means of all four sequences that is Empa administered before or after the administration of either TOR, HCT and their combination with Empa" (NCT01276288)
Timeframe: baseline and then day 6 for Empa, day 5 for TOR and HCT, day 10 for Empa+TOR and Empa+HCT

InterventionmOsm/kg (Mean)
Empagliflozin (Empa)223.15
Hydrochlorothiazide (HCT)-3.900
Torasemide (TOR)-5.800
Empa+ HCT217.700
Empa + TOR330.400

Change in Urine pH From Baseline

"Change in urine pH from baseline, where baseline was defined as the measurement obtained before first drug administration in the first period~The mean change from baseline was evaluated as:~Empa: day 6- baseline, HCT: day 5-baseline, TOR: day 5-baseline, Empa+ HCT: day 10- baseline, Empa+ TOR: day 10- baseline,~The mean for the Empa arm represent combined adjusted means of all four sequences that is Empa administered before or after the administration of either TOR, HCT and their combination with Empa" (NCT01276288)
Timeframe: baseline and then day 6 for Empa, day 5 for TOR and HCT, day 10 for Empa+TOR and Empa+HCT

InterventionpH (Mean)
Empagliflozin (Empa)-0.132
Hydrochlorothiazide (HCT)-0.452
Torasemide (TOR)-0.147
Empa+ HCT-0.448
Empa + TOR0.130

Maximum Measured Concentration of Empa in Plasma (Cmax, ss)

Maximum measured concentration of Empa in plasma (Cmax, ss) at steady state (NCT01276288)
Timeframe: Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 16, and 24 post-dose on Day 5 with EMPA alone and on Day 9 with EMPA plus diuretic. The Pre-dose values were averaged over Days 1 to 4 with EMPA alone and on Days 7 & 8 with EMPA plus diuretic

Interventionnmol/L (Geometric Mean)
Empagliflozin (Empa)939
Empa+ HCT1030
Empa + TOR949

Maximum Measured Concentration of HCT in Plasma (Cmax, ss)

Maximum measured concentration of HCT in plasma (Cmax, ss) at steady state (NCT01276288)
Timeframe: Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 16, and 24 post-dose on Day 4 with HCT alone and on Day 9 with EMPA plus HCT. The Pre-dose values were averaged over Days 1 to 3 with HCT alone and on Days 7 & 8 with EMPA plus HCT

Interventionng/mL (Geometric Mean)
Hydrochlorothiazide (HCT)203
HCT+ Empa205

Maximum Measured Concentration of TOR in Plasma (Cmax, ss)

Maximum measured concentration of Empa in plasma (Cmax, ss) at steady state (NCT01276288)
Timeframe: Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 16, and 24 post-dose on Day 4 with TOR alone and on Day 9 with EMPA plus TOR. The Pre-dose values were averaged over Days 1 to 3 with TOR alone and on Days 7 & 8 with EMPA plus TOR

Interventionng/mL (Geometric Mean)
Torasemide (TOR)710
TOR+ Empa741
TOR Metabolite (TOR-M1)42.6
TOR Metabolite (TOR-M3)8.58
TOR-M1+ Empa43.8
TOR-M3 + Empa8.79

Number of Subjects With Clinical Relevant Abnormalities in Vital Signs, Clinical Laboratory Tests, 12-lead Resting Electrocardiogram (ECG), Physical Examination and Assessment of Tolerability by the Investigator

"Number of subjects with clinical relevant abnormalities in vital signs (blood pressure, pulse rate), 12-lead resting electrocardiogram (ECG), clinical laboratory tests (haematology, clinical chemistry, urinalysis, and monitoring of fasting plasma glucose), physical examination and assessment of tolerability by the investigator.~New abnormal findings were reported as Adverse Events (AE). Only Alanine aminotransferase normal under system organ class investigations was determined as an existing AE." (NCT01276288)
Timeframe: From first drug administration until up to 14 days after the last drug administration, up to 35 days

Interventionparticipants (Number)
Empagliflozin (Empa)1
Hydrochlorothiazide (HCT)0
Torasemide (TOR)0
Empa+ HCT0
Empa + TOR0

The Change in Micturition Frequency From the Baseline

For this endpoint the change in total micturition frequency from the baseline was only examined for EMPA where baseline was defined as the day before the first drug administration. (NCT01276288)
Timeframe: Baseline and day 5

Interventionvoids per day (Mean)
Empagliflozin (Empa)1.600

The Change in Total Muscle Sympathetic Nerve Activity (MSNA) From Off- Treatment

The change in total Muscle sympathetic nerve activity (MSNA) that represents an area under the curve of all C-fiber action potentials per minute. This endpoint was evaluated only for Empa. For this endpoint a baseline value was not defined. However, the parameters obtained at 2 measurements time points during the trial were compared. (NCT01276288)
Timeframe: One day before the drug administration, then day 4 after the first drug administration

Interventionaction potentials per min (Mean)
Empagliflozin (Empa)0.241

Change in Clearance of Sodium, Potassium, Creatinine, Magnesium, Chloride,Calcium, Phosphate and Uric Acid From Baseline

"Change in clearance of sodium, potassium, creatinine, magnesium, chloride,calcium, phosphate and uric acid from baseline, where baseline is defined as the value obtained from the last 24-h collection period before the first drug administration in the first treatment period.~The mean change from baseline was evaluated as:~Empa: day 5- baseline, HCT: day 4-baseline, TOR: day 4-baseline, Empa+ HCT: day 9- baseline, Empa+ TOR: day 9- baseline,~The means for the Empa arm represent combined adjusted means of all four sequences that is Empa administered before or after the administration of either TOR, HCT and their combination with Empa" (NCT01276288)
Timeframe: 24 hour sampling interval at baseline and then day 5 for Empa, day 4 for TOR and HCT, day 9 for Empa+TOR and Empa+HCT

,,,,
Interventionml/min (Mean)
SodiumChloridePotassiumMagnesiumCalciumPhosphateUric AcidCreatinine
Empa + TOR-0.004-0.1172.3240.209-0.1742.3594.359-11.768
Empa+ HCT0.1430.1144.1251.115-0.4072.7955.065-10.126
Empagliflozin (Empa)-0.031-0.1292.0400.398-0.3265.2756.3773.167
Hydrochlorothiazide (HCT)-0.055-0.0582.2051.826-0.2994.633-0.476-7.034
Torasemide (TOR)-0.071-0.157-0.5181.148-0.0654.368-1.310-4.250

Change in Serum Concentration of Creatinine and Uric Acid From Baseline

"Change in serum concentration of Creatinine and Uric acid from baseline, where baseline was defined as the measurement obtained before first drug administration in the first period~The mean change from baseline was evaluated as:~Empa: day 5- baseline, HCT: day 4-baseline, TOR: day 4-baseline, Empa+ HCT: day 9- baseline, Empa+ TOR: day 9- baseline,~The means for the Empa arm represent combined adjusted means of all four sequences that is Empa administered before or after the administration of either TOR, HCT and their combination with Empa" (NCT01276288)
Timeframe: baseline and then day 5 for Empa, day 4 for TOR and HCT, day 9 for Empa+TOR and Empa+HCT

,,,,
Interventionumol/L (Mean)
CreatinineUric acid
Empa + TOR3.570-48.200
Empa+ HCT6.280-31.000
Empagliflozin (Empa)2.175-64.950
Hydrochlorothiazide (HCT)-0.34024.200
Torasemide (TOR)-2.180-4.700

Change in Serum Concentration of Renin, Intact Parathyroid Hormone (iPTH) and 1,25-dihydroxyvitamin D From Baseline

"Change in serum concentration of Renin, intact parathyroid hormone (iPTH) and 1,25-dihydroxyvitamin D from baseline , where baseline was defined as the measurement obtained before first drug administration in the first period~The mean change from baseline was evaluated as:~Empa: day 6- baseline, HCT: day 5-baseline, TOR: day 5-baseline, Empa+ HCT: day 10- baseline, Empa+ TOR: day 10- baseline,~The means for the Empa arm represent combined adjusted means of all four sequences that is Empa administered before or after the administration of either TOR, HCT and their combination with Empa" (NCT01276288)
Timeframe: baseline and then day 6 for Empa, day 5 for TOR and HCT, day 10 for Empa+TOR and Empa+HCT

,,,,
Interventionpg/mL (Mean)
ReniniPTH1,25-dihydroxyvitamin D
Empa + TOR17.05012.190-0.970
Empa+ HCT32.7609.280-5.060
Empagliflozin (Empa)-0.9608.2650.230
Hydrochlorothiazide (HCT)16.1506.1601.560
Torasemide (TOR)2.5506.9103.530

Change in Serum Concentration of Sodium, Potassium, Magnesium, Calcium, Chloride, Phosphate, Glucose and Urea From Baseline

"Change in serum concentration of sodium, potassium, magnesium, calcium, chloride, phosphate, glucose and urea from baseline, where baseline was defined as the measurement obtained before first drug administration in the first period~The mean change from baseline was evaluated as:~Empa: day 6- baseline, HCT: day 5-baseline, TOR: day 5-baseline, Empa+ HCT: day 10- baseline, Empa+ TOR: day 10- baseline,~The means for the Empa arm represent combined adjusted means of all four sequences that is Empa administered before or after the administration of either TOR, HCT and their combination with Empa" (NCT01276288)
Timeframe: baseline and then day 6 for Empa, day 5 for TOR and HCT, day 10 for Empa+TOR and Empa+HCT

,,,,
Interventionmmol/L (Mean)
SodiumPotassiumMagnesiumChlorideCalciumPhosphateUreaGlucose
Empa + TOR1.600-0.3600.1452.100-0.0600.0502.122-0.526
Empa+ HCT-0.100-0.5300.130-3.200-0.0100.1701.504-0.033
Empagliflozin (Empa)1.500-0.1700.1392.050-0.0550.0450.710-1.123
Hydrochlorothiazide (HCT)-0.500-0.4700.025-2.600-0.0400.0600.6500.849
Torasemide (TOR)0.200-0.2000.0591.000-0.080-0.0600.3180.527

Change in Urinary Excretion in a 24-hour Period of Sodium, Potassium, Magnesium, Chloride, Calcium, Phosphate, Creatinine, Uric Acid, Glucose From Baseline

"Change in urinary excretion in a 24-hour period of sodium, potassium, magnesium, chloride, calcium, phosphate, creatinine, uric acid, glucose from baseline, where baseline was defined as the value obtained from the last 24-hour (h) collection period before the first drug administration in the first treatment period. This applies also to sodium excretion in urine, which is additionally obtained one day before the drug administration before the second period.~The mean change from baseline was evaluated as:~Empa: day 5- baseline, HCT: day 4-baseline, TOR: day 4-baseline, Empa+ HCT: day 9- baseline, Empa+ TOR: day 9- baseline,~The means for the Empa arm represent combined adjusted means of all four sequences that is Empa administered before or after the administration of either TOR, HCT and their combination with Empa" (NCT01276288)
Timeframe: 24 hour sampling interval at baseline and then day 5 for Empa, day 4 for TOR and HCT, day 9 for Empa+TOR and Empa+HCT

,,,,
Interventionmmol/day (Mean)
SodiumChloridePotassiumMagnesiumCalciumPhosphateCreatinineUric acidGlucose
Empa + TOR1.200-14.6008.4601.050-0.7405.000-0.0401.244740.910
Empa+ HCT28.90011.40015.7902.030-1.3608.3000.0221.555685.233
Empagliflozin (Empa)-4.300-16.30010.3701.190-1.1609.2500.0911.641599.449
Hydrochlorothiazide (HCT)-11.700-12.3006.2002.270-1.0209.000-0.078-0.03717.584
Torasemide (TOR)-13.700-22.000-6.9901.720-0.4304.900-0.073-0.50017.932

Changes in Bicarbonate Concentrations of Calcium, Bicarbonate Ions and Base Excess in Capillary or Arterialised Blood From Baseline

"Changes in bicarbonate concentrations of calcium, bicarbonate ions and base excess in capillary or arterialised blood from baseline, where baseline was defined as the last measurement before trial drug administration of each treatment period~The mean change from baseline was evaluated as:~Empa: day 6- baseline, HCT: day 5-baseline, TOR: day 5-baseline, Empa+ HCT: day 10- baseline, Empa+ TOR: day 10- baseline,~The means for the Empa arm represent combined adjusted means of all four sequences that is Empa administered before or after the administration of either TOR, HCT and their combination with Empa" (NCT01276288)
Timeframe: baseline and then day 6 for Empa, day 5 for TOR and HCT, day 10 for Empa+TOR and Empa+HCT

,,,,
Interventionmmol/ L (Mean)
Bicarbonate concentrations of calciumbicarbonate ionsBase excess
Empa + TOR-1.590-0.049-1.450
Empa+ HCT1.860-0.0531.720
Empagliflozin (Empa)-1.090-0.049-1.045
Hydrochlorothiazide (HCT)2.020-0.0431.640
Torasemide (TOR)-0.400-0.041-0.420

Urinary Sodium Excretion Over 24-hour run-in Periods

Urinary sodium excretion over 24-hour run-in periods to assess the harmonisation of electrolytes after intake of a standardised diet (NCT01276288)
Timeframe: Day 3, 2 and 1 before the first drug administration

,,
Interventionmmol/day (Mean)
3 days before the drug administration2 days before the drug administration1 day before the drug administration
Empagliflozin (Empa)198.50174.35163.90
Hydrochlorothiazide (HCT)211.10183.30170.10
Torasemide (TOR)217.90178.70179.10

Independent Re-adjudication (IR) Outcome: Number of Participants With a First Occurrence of a Major Adverse Cardiovascular Event (MACE) Defined as CV (or Unknown) Death, Non-fatal MI, and Non-fatal Stroke Based on Original RECORD Endpoint Definitions

IR was based on original RECORD endpoint definitions. CV death= no unequivocal non-CV cause (sudden death, death from acute vascular events, heart failure, acute MI, other CV causes, and deaths adjudicated as unknown cause). MI event=hospitalization + elevation of specific cardiac biomarkers above the upper limit of normal + cardiac ischemia symptoms/new pathological electrocardiogram findings. Stroke event=hospitalization + rapidly developed clinical signs of focal/global disturbance of cerebral function for more than 24 hours, with no apparent cause other than a vascular origin. (NCT00379769)
Timeframe: Baseline through End of Study (up to 7.5 years)

Interventionparticipants (Number)
Combined RSG181
Combined MET/SU188

Independent Re-adjudication Outcome: Number of Participants (Par.) With an Event of Stroke (Fatal and Non-fatal), Based on Original RECORD Endpoint Definitions

Par. with a stroke (fatal or non-fatal) event as determined by independent re-adjudication using the original RECORD endpoint definitions was recorded. A stroke event=hospitalization plus rapidly developed clinical signs of focal (or global) disturbance of cerebral function lasting more than 24 hours (unless interrupted by thrombolysis, surgery, or death), with no apparent cause other than a vascular origin, including par. presenting clinical signs/symptoms suggestive of subarachnoid haemorrhage/intracerebral haemorrhage/cerebral ischemic necrosis or cause of death adjudicated as stroke. (NCT00379769)
Timeframe: Baseline through End of Study (up to 7.5 years)

Interventionparticipants (Number)
Combined RSG50
Combined MET/SU63

Independent Re-adjudication Outcome: Number of Participants Who Died Due to Any Cause

All deaths identified during the original record study and discovered after the re-adjudication efforts began were included. (NCT00379769)
Timeframe: Baseline through End of Study (up to 7.5 years)

Interventionparticipants (Number)
Combined RSG139
Combined MET/SU160

Independent Re-adjudication Outcome: Number of Participants With a CV (or Unknown) Death, Based on Contemporary Endpoint Definitions

The number of participants with a CV (or unknown) death as determined by independent re-adjudication using the Standard Data Collection for Cardiovascular Trials Initiative (draft October 2011) endpoint definitions was recorded. CV death included death resulting from an acute myocardial infarction (MI), sudden cardiac death, death due to heart failure, death due to stroke, and death due to other CV causes. Deaths of unknown cause were counted as CV deaths. (NCT00379769)
Timeframe: Baseline through End of Study (up to 7.5 years)

Interventionparticipants (Number)
Combined RSG88
Combined MET/SU96

Independent Re-adjudication Outcome: Number of Participants With a CV (or Unknown) Death, Based on Original RECORD Endpoint Definitions

"The number of participants with a CV death (or unknown) as determined by independent re-adjudication using the original RECORD endpoint definitions was recorded. CV death was defined as any death for which an unequivocal non-CV cause could not be established. CV death included death following heart failure, death following acute myocardial infarction (MI), sudden death, death due to acute vascular events, and other CV causes. Deaths due to unknown causes were classified as unknown deaths, but were counted as CV deaths for the analysis of this endpoint." (NCT00379769)
Timeframe: Baseline through End of Study (up to 7.5 years)

Interventionparticipants (Number)
Combined RSG88
Combined MET/SU96

Independent Re-adjudication Outcome: Number of Participants With a First Occurrence of a Major Adverse Cardiovascular Event (MACE) Defined as CV (or Unknown) Death, Non-fatal MI, and Non-fatal Stroke Based on Contemporary Endpoint Definitions

Independent re-adjudication was based on the Standard Data Collection for Cardiovascular Trials Initiative (draft October 2011) endpoint definitions. CV death included death resulting from an acute MI; sudden cardiac death and death due to heart failure, stroke, and to other CV causes. Deaths of unknown cause were counted as CV deaths. MI was defined as evidence of myocardial necrosis in a clinical setting consistent with myocardial ischemia. Stroke was defined as an acute episode of neurological dysfunction caused by focal or global brain, spinal cord, or retinal vascular injury. (NCT00379769)
Timeframe: Baseline through End of Study (up to 7.5 years)

Interventionparticipants (Number)
Combined RSG186
Combined MET/SU191

Independent Re-adjudication Outcome: Number of Participants With an Event of Myocardial Infarction (Fatal and Non-fatal), Based on Contemporary Endpoint Definitions

The number of participants with an MI (fatal or non-fatal) event as determined by independent re-adjudication using the Standard Data Collection for Cardiovascular Trials Initiative (draft October 2011) endpoint definitions was recorded. An event of MI was defined as evidence of myocardial necrosis in a clinical setting consistent with myocardial ischemia. (NCT00379769)
Timeframe: Baseline through End of Study (up to 7.5 years)

Interventionparticipants (Number)
Combined RSG72
Combined MET/SU62

Independent Re-adjudication Outcome: Number of Participants With an Event of Myocardial Infarction (Fatal and Non-fatal), Based on Original RECORD Endpoint Definitions

The number of participants with an MI (fatal or non-fatal) event as determined by independent re-adjudication using the original RECORD endpoint definitions was recorded. An event of MI was defined as hospitalization plus elevation of cardiac biomarkers troponin (TN) I and/or TNT above the upper limit of normal (ULN) or creatinine kinase (CK) MB (M=muscle type; B=brain type) isoenzyme >= 2x the ULN or CK > 2x the ULN plus typical symptoms of cardiac ischemia or new pathological electrocardiogram findings, or cause of death adjudicated as MI. (NCT00379769)
Timeframe: Baseline through End of Study (up to 7.5 years)

Interventionparticipants (Number)
Combined RSG68
Combined MET/SU60

Independent Re-adjudication Outcome: Number of Participants With an Event of Stroke (Fatal and Non-fatal), Based on Contemporary Endpoint Definitions

The number of participants with a stroke (fatal or non-fatal) event as determined by independent re-adjudication using the Standard Data Collection for Cardiovascular Trials Initiative (draft October 2011) endpoint definitions was recorded. An event of stroke was defined as an acute episode of neurological dysfunction caused by focal or global brain, spinal cord, or retinal vascular injury. (NCT00379769)
Timeframe: Baseline through End of Study (up to 7.5 years)

Interventionparticipants (Number)
Combined RSG53
Combined MET/SU64

Model Adjusted Change From Baseline in Alanine Aminotransferase at Month 60

Model adjusted (adjusted for any imbalances in the baseline values between within stratum treatment groups) change from baseline in alanine aminotransferase was calculated as the value at Month 60 minus the Baseline value. (NCT00379769)
Timeframe: Baseline to Month 60 of the randomised dual therapy treatment phase

InterventionU/L (Units/Liter) (Mean)
RSG in Addition to Background MET-37.43
SU in Addition to Background MET-21.73
RSG in Addition to Background SU-30.17
MET in Addition to Background SU-24.00

Model Adjusted Change From Baseline in Body Weight at Month 60

Model adjusted (adjusted for any imbalances in the baseline values between within stratum treatment groups) change from baseline in body weight was calculated as the value at Month 60 minus the Baseline value. (NCT00379769)
Timeframe: Baseline to Month 60 of the randomised dual therapy treatment phase

Interventionkilograms (Mean)
RSG in Addition to Background MET3.93
SU in Addition to Background MET-0.54
RSG in Addition to Background SU4.72
MET in Addition to Background SU-2.16

Model Adjusted Change From Baseline in Fasting Plasma Glucose at Month 60

Model adjusted (adjusted for any imbalances in the baseline values between within stratum treatment groups) change from baseline in fasting plasma glucose was calculated as the value at Month 60 minus the Baseline value. (NCT00379769)
Timeframe: Baseline to Month 60 of the randomised dual therapy treatment period

Interventionmmol/L (millimoles/Liter) (Mean)
RSG in Addition to Background MET-1.38
SU in Addition to Background MET-0.29
RSG in Addition to Background SU-2.00
MET in Addition to Background SU-0.94

Model Adjusted Change From Baseline in HbA1c at Month 60

Model adjusted (adjusted for any imbalances in the baseline values between within stratum treatment groups) change from baseline in HbA1c was calculated as the value at Month 60 minus the Baseline value. (NCT00379769)
Timeframe: Baseline and Month 60 of randomised dual therapy treatment period

InterventionPercent (Mean)
RSG in Addition to Background MET-0.14
SU in Addition to Background MET0.17
RSG in Addition to Background SU-0.24
MET in Addition to Background SU-0.10

Model Adjusted Change From Baseline in Waist Circumference at Month 60

Model adjusted (adjusted for any imbalances in the baseline values between within stratum treatment groups) change from baseline in waist circumference was calculated as the value at Month 60 minus the Baseline value. (NCT00379769)
Timeframe: Baseline to Month 60 of the randomised dual therapy treatment phase

Interventioncm (centimeters) (Mean)
RSG in Addition to Background MET2.70
SU in Addition to Background MET0.65
RSG in Addition to Background SU3.00
MET in Addition to Background SU-0.60

Model Adjusted Ratio to Baseline (Expressed as a Percentage) for Apolipoprotein B (Apo-B) at Month 60

The model adjusted (adjusted for any imbalances in the baseline [BL] values between within stratum treatment groups) ratio to BL in Apo-B was calculated as the ratio of the Month 60 value to the BL value and was expressed as percent change from BL. For each treatment group, the model-adjusted mean change from BL at Month 60 was determined on the log scale. This mean was then back transformed to give a geometric mean (GM) of the ratio of the Month 60 value to BL on the original scale. The GM was expressed as a percentage (100*[GM^-1]). (NCT00379769)
Timeframe: Baseline to Month 60 of the randomised dual therapy treatment period

Interventionpercent change (Geometric Mean)
RSG in Addition to Background MET-13.77
SU in Addition to Background MET-11.63
RSG in Addition to Background SU-9.68
MET in Addition to Background SU-12.09

Model Adjusted Ratio to Baseline (Expressed as a Percentage) for C-Reactive Protein at Month 60

The model adjusted (adjusted for any imbalances in the baseline [BL] values between within stratum treatment groups) ratio to BL in C-Reactive Protein was calculated as the ratio of the Month 60 value to the BL value and was expressed as percent change from BL. For each treatment group, the model-adjusted mean change from BL at Month 60 was determined on the log scale. This mean was then back transformed to give a geometric mean (GM) of the ratio of the Month 60 value to BL on the original scale. The GM was expressed as a percentage (100*[GM^-1]). (NCT00379769)
Timeframe: Baseline to Month 60 of the randomised dual therapy treatment phase

Interventionpercent change (Geometric Mean)
RSG in Addition to Background MET-57.40
SU in Addition to Background MET-28.92
RSG in Addition to Background SU-56.50
MET in Addition to Background SU-36.29

Model Adjusted Ratio to Baseline (Expressed as a Percentage) for Fibrinogen at Month 60

The model adjusted (adjusted for any imbalances in the baseline [BL] values between within stratum treatment groups) ratio to BL in fibrinogen was calculated as the ratio of the Month 60 value to the BL value and was expressed as percent change from BL. For each treatment group, the model-adjusted mean change from BL at Month 60 was determined on the log scale. This mean was then back transformed to give a geometric mean (GM) of the ratio of the Month 60 value to BL on the original scale. The GM was expressed as a percentage (100*[GM^-1]). (NCT00379769)
Timeframe: Baseline to Month 60 of the randomised dual therapy treatment phase

Interventionpercent change (Geometric Mean)
RSG in Addition to Background MET2.12
SU in Addition to Background MET5.74
RSG in Addition to Background SU-0.23
MET in Addition to Background SU3.14

Model Adjusted Ratio to Baseline (Expressed as a Percentage) for Plasminogen Activator Inhibitor-1 (PAI-1) Antigen at Month 60

The model adjusted (adjusted for any imbalances in the baseline [BL] values between within stratum treatment groups) ratio to BL in plasminogen activator inhibitor-1 (PAI-1) antigen was calculated as the ratio of the Month 60 value to the BL value and was expressed as percent change from BL. For each treatment group, the model-adjusted mean change from BL at Month 60 was determined on the log scale. This mean was then back transformed to give a geometric mean (GM) of the ratio of the Month 60 value to BL on the original scale. The GM was expressed as a percentage (100*[GM^-1]). (NCT00379769)
Timeframe: Baseline to Month 60 of the randomised dual therapy treatment phase

Interventionpercent change (Geometric Mean)
RSG in Addition to Background MET-9.85
SU in Addition to Background MET15.01
RSG in Addition to Background SU-7.79
MET in Addition to Background SU-0.64

Model Adjusted Ratio to Baseline (Expressed as a Percentage) for Urinary Albumin Creatinine Ratio at Month 60

The model adjusted (adjusted for any imbalances in the baseline [BL] values between within stratum treatment groups) ratio to BL in urinary albumin creatinine ratio was calculated as the ratio of the Month 60 value to the BL value and was expressed as percent change from BL. For each treatment group, the model-adjusted mean change from BL at Month 60 was determined on the log scale. This mean was then back transformed to give a geometric mean (GM) of the ratio of the Month 60 value to BL on the original scale. The GM was expressed as a percentage (100*[GM^-1]). (NCT00379769)
Timeframe: Baseline to Month 60 of the randomised dual therapy treatment phase

Interventionpercent change (Geometric Mean)
RSG in Addition to Background MET8.31
SU in Addition to Background MET15.17
RSG in Addition to Background SU-3.43
MET in Addition to Background SU11.91

Number of Participants With an Event of Death Due to a Bone Fracture-related Event: Main Study + Observational Follow-up Combined

The observational follow-up was designed to collect data concerning cancer and bone fractures in RECORD participants during a 4-year period after the end of the main RECORD study. At the end of the main study, all study medication was stopped. Participants were not provided with study medication in the observational follow-up; instead, anti-diabetic treatment was prescribed at the investigator's discretion. A bone fracture event is defined as one or more fractured bones occurring on the same date and that had the same Higher Level Group Term (HLGT) for fracture location, per participant. (NCT00379769)
Timeframe: From the beginning of the main study through the end of the observational follow-up (up to 11.4 years)

Interventionparticipants (Number)
Combined RSG: Main Study and Observational Follow-up0
Combined MET/SU: Main Study and Observational Follow-up0

Number of Participants With Cardiovascular Death/Cardiovascular Hospitalisation Events

The number of participants with cardiovascular death events (death due to cardiovascular causes or deaths with insufficient information to rule out a cardiovascular cause) and cardiovascular hospitalisation events (hospitalisation for a cardiovascular event, excluding planned admissions not associated with a worsening of the disease/condition of the participant) was recorded. (NCT00379769)
Timeframe: Baseline through End of Study (up to 7.5 years)

Interventionparticipants (Number)
Combined RSG321
Combined MET/SU323

Number of Participants With First Cardiovascular Hospitalisations/Cardiovascular Deaths by Stratum

Participants with first cardiovascular death (death due to cardiovascular causes or deaths with insufficient information to rule out a cardiovascular cause) and cardiovascular hospitalisation (hospitalisation for a cardiovascular event, excluding planned admissions not associated with a worsening of the disease/condition of the participant) were recorded by study stratum. (NCT00379769)
Timeframe: Baseline through End of Study (up to 7.5 years)

Interventionpartcipants (Number)
RSG in Addition to Background MET158
SU in Addition to Background MET154
RSG in Addition to Background SU163
MET in Addition to Background SU169

Number of Participants With Glycaemic Failure Events

Failure of glycaemic control was defined as two consecutive HbA1c values of ≥8.5 percent, or HbA1c ≥8.5percent at a single visit, after which the subject was either moved to the post-randomised treatment phase or triple therapy was started. (NCT00379769)
Timeframe: Baseline through to end of randomised dual therapy

Interventionparticipants (Number)
RSG in Addition to Background MET281
SU in Addition to Background MET451
RSG in Addition to Background SU365
MET in Addition to Background SU424

The Number of Participants Starting Insulin at Any Time During the Study

The number of participants starting insulin at any time during the study was recorded. (NCT00379769)
Timeframe: Baseline through End of Study (up to 7.5 years)

Interventionparticipants (Number)
RSG in Addition to Background MET126
SU in Addition to Background MET276
RSG in Addition to Background SU168
MET in Addition to Background SU259

Model Adjusted Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at Month 60

Model adjusted (adjusted for any imbalances in the baseline values between within treatment groups) change from baseline in SBP and DBP was calculated as the value at Month 60 minus the Baseline value. (NCT00379769)
Timeframe: Baseline to Month 60 of the randomised dual therapy treatment phase

,,,
InterventionmmHg (millimeters of mercury) (Mean)
SBPDBP
MET in Addition to Background SU-0.6-2.3
RSG in Addition to Background MET-1.9-3.6
RSG in Addition to Background SU-2.3-3.6
SU in Addition to Background MET-2.2-3.4

Model Adjusted Mean Change From Baseline in Insulin and Pro-insulin at Month 60

Model adjusted (adjusted for any imbalances in the baseline values between within stratum treatment groups) change from baseline in insulin and pro-insulin was calculated as the value at Month 60 minus the Baseline value. (NCT00379769)
Timeframe: Baseline to Month 60 of the randomised dual therapy treatment period

,,,
Interventionpicamoles/liter (pmol/L) (Mean)
Insulin, Adjusted Change from BaselinePro-insulin, Adjusted Change from Baseline
MET in Addition to Background SU-12.1-3.0
RSG in Addition to Background MET-18.6-2.4
RSG in Addition to Background SU-16.9-3.2
SU in Addition to Background MET3.74.2

Model Adjusted Ratio to Baseline (Expressed as a Percentage) for Total Cholesterol (TC), Low-density Lipoprotein (LDL) Cholesterol, High-density Lipoprotein (HDL) Cholesterol, Triglycerides, and Free Fatty Acids (FFAs) at Month 60

The model adjusted (adjusted for any imbalances in the baseline [BL] values between within stratum treatment groups) ratio to BL in TC, LDL cholesterol, HDL cholesterol, triglycerides, and FFAs was calculated as the ratio of the Month 60 value to the BL value and was expressed as percent change from BL. For each treatment group, the model-adjusted mean change from BL at Month 60 was determined on the log scale. This mean was then back transformed to give a geometric mean (GM) of the ratio of the Month 60 value to BL on the original scale. The GM was expressed as a percentage (100*[GM^-1]). (NCT00379769)
Timeframe: Baseline to Month 60 of the randomised dual therapy treatment phase

,,,
Interventionpercent change (Geometric Mean)
Total cholesterolHDL-cholesterolLDL-cholesterolTriglyceridesFree fatty acids
MET in Addition to Background SU-9.686.14-17.80-2.504.47
RSG in Addition to Background MET-5.499.95-12.70-7.97-16.46
RSG in Addition to Background SU-2.917.73-8.99-2.68-11.58
SU in Addition to Background MET-9.092.57-17.68-1.952.79

Model Adjusted Ratio to Baseline (Expressed as a Percentage) for Total Cholesterol (TC):High-density Lipoprotein (HDL) Cholesterol and Low-density Lipoprotein (LDL) Cholesterol:HDL Cholesterol Ratios at Month 60

The model adjusted (adjusted for any imbalances in the baseline [BL] values between within stratum treatment groups) ratio to BL in TC:HDL cholesterol and LDL cholesterol:HDL cholesterol was calculated as the ratio of the Month 60 value to the BL value and was expressed as percent change from BL. For each treatment group, the model-adjusted mean change from BL at Month 60 was determined on the log scale. This mean was then back transformed to give a geometric mean (GM) of the ratio of the Month 60 value to BL on the original scale. The GM was expressed as a percentage (100*[GM^-1]). (NCT00379769)
Timeframe: Baseline to Month 60 of the randomised dual therapy treatment period

,,,
Interventionpercent change (Geometric Mean)
Total Cholesterol: HDL Cholesterol RatioLDL Cholesterol: HDL-Cholesterol Ratio
MET in Addition to Background SU-15.01-22.53
RSG in Addition to Background MET-14.20-20.89
RSG in Addition to Background SU-9.93-15.85
SU in Addition to Background MET-11.33-20.04

Model Adjusted Ratio to Baseline (Expressed as a Percentage) Homeostasis Model Assessment (HOMA) Beta Cell Function and Insulin Sensitivity at Month 60

The model adjusted (adjusted for any imbalances in the baseline [BL] values between within stratum treatment groups) ratio to BL in HOMA beta-cell function and insulin sensitivity was calculated as the ratio of the Month 60 value to the BL value and was expressed as percent change from BL. For each treatment group, the model-adjusted mean change from BL at Month 60 was determined on the log scale. This mean was then back transformed to give a geometric mean (GM) of the ratio of the Month 60 value to BL on the original scale. The GM was expressed as a percentage (100*[GM^-1]). (NCT00379769)
Timeframe: Baseline to Month 60 of the randomised dual therapy treatment phase

,,,
Interventionpercent change (Geometric Mean)
Beta cell functionInsulin sensitivity
MET in Addition to Background SU12.4323.90
RSG in Addition to Background MET20.5442.57
RSG in Addition to Background SU32.3542.07
SU in Addition to Background MET19.28-3.45

Number of Bone Fracture Events With the Indicated Outcome: Main Study + Observational Follow-up Combined

"The observational follow-up was designed to collect data concerning cancer and bone fractures in RECORD participants during a 4-year period after the end of the main RECORD study. At the end of the main study, all study medication was stopped. Participants were not provided with study medication in the observational follow-up; instead, anti-diabetic treatment was prescribed at the investigator's discretion. A bone fracture event is defined as one or more fractured bones occurring on the same date and that had the same Higher Level Group Term (HLGT) for fracture location, per participant. The indicated fracture outcome was pre-specified in the CRF and included Unknown as a category. Fracture events with missing outcome data were reported as Data unavailable." (NCT00379769)
Timeframe: From the beginning of the main study through the end of the observational follow-up (up to 11.4 years)

,
Interventionbone fracture events (Number)
Number of bone fracture eventsUnknownNormal healing with standard managementComplicationAdditional therapeutic measures requiredData unavailable
Combined MET/SU: Main Study and Observational Follow-up17451421395
Combined RSG: Main Study and Observational Follow-up2997250141612

Number of Bone Fracture Events With the Indicated Outcome: Observational Follow-up

"The observational follow-up was designed to collect data concerning cancer and bone fractures in RECORD participants during a 4-year period after the end of the main RECORD study. At the end of the main study, all study medication was stopped. Participants were not provided with study medication in the observational follow-up; instead, anti-diabetic treatment was prescribed at the investigator's discretion. A bone fracture event is defined as one or more fractured bones occurring on the same date and that had the same Higher Level Group Term (HLGT) for fracture location, per participant. The indicated fracture outcome was pre-specified in the CRF and included Unknown as a category. Fracture events with missing outcome data were reported as Data unavailable." (NCT00379769)
Timeframe: From the end of the RECORD study through the end of the observational follow-up (up to 4.0 years)

,
Interventionbone fracture events (Number)
Number of bone fracture eventsUnknownNormal healing with standard managementComplicationAdditional therapeutic measures requiredData unavailable
Combined MET/SU: Observational Follow-up41133421
Combined RSG: Observational Follow-up70151738

Number of HbA1c and Fasting Plasma Glucose (FPG) Responders at Month 60

Number of responders, i.e., participants meeting glycaemic targets (HbA1c less than or equal to 7 percent, FPG less than or equal to 7 mmol/L) (NCT00379769)
Timeframe: Baseline to Month 60 of the randomised dual therapy treatment period

,,,
Interventionparticipants (Number)
HbA1c RespondersFPG Responders
MET in Addition to Background SU180154
RSG in Addition to Background MET265300
RSG in Addition to Background SU235257
SU in Addition to Background MET208180

Number of Participants Who Died Due to the Indicated Cancer-related Event: Main Study + Observational Follow-up Combined

The observational follow-up was designed to collect data concerning cancer and bone fractures in RECORD participants during a 4-year period after the end of the main RECORD study. At the end of the main study, all study medication was stopped. Participants were not provided with study medication in the observational follow-up; instead, anti-diabetic treatment was prescribed at the investigator's discretion. An SAE is defined as any event that is fatal; life threatening; disabling/incapacitating; results in hospitalization (excluding elective surgery or routine clinical procedures); prolongs a hospital stay; is associated with a congenital abnormality; cancer; is associated with an overdose. In addition, any event that the investigator regards as serious or that would suggest any significant hazard, contraindication, side effect, or precaution that may be associated with the study procedures should be reported as an SAE. (NCT00379769)
Timeframe: From the beginning of the main study through the end of the observational follow-up (up to 11.4 years)

,
Interventionparticipants (Number)
Any cancer-related deathAny gastrointestinal eventPancreaticColon/rectalGastricLiverGall bladder/biliaryGastrointestinal event; not specifiedAny genitourinary eventRenalUterineProstateBladderOvarianLungAny hematologic eventSkin (melanoma)Skin (non-melanomatous)MetastasesBreastHead and neckAny neurologic eventEndocrineNot specified
Combined MET/SU: Main Study and Observational Follow-up723412113431153523211000432201
Combined RSG: Main Study and Observational Follow-up592546744062111113431221210

Number of Participants Who Died Due to the Indicated Cancer-related Event: Observational Follow-up

The observational follow-up was designed to collect data concerning cancer and bone fractures in RECORD participants during a 4-year period after the end of the main RECORD study. At the end of the main study, all study medication was stopped. Participants were not provided with study medication in the observational follow-up; instead, anti-diabetic treatment was prescribed at the investigator's discretion. An SAE is defined as any event that is fatal; life threatening; disabling/incapacitating; results in hospitalization (excluding elective surgery or routine clinical procedures); prolongs a hospital stay; is associated with a congenital abnormality; cancer; is associated with an overdose. In addition, any event that the investigator regards as serious or that would suggest any significant hazard, contraindication, side effect, or precaution that may be associated with the study procedures should be reported as an SAE. (NCT00379769)
Timeframe: From the end of the RECORD study through the end of the observational follow-up (up to 4.0 years)

,
Interventionparticipants (Number)
Any cancer-related deathAny gastrointestinal eventPancreaticColon/rectalGastricLiverGall bladder/biliaryGastrointestinal event; not specifiedAny genitourinary eventRenalUterineProstateBladderOvarianLungAny hematologic eventSkin (melanoma)Skin (non-melanomatous)MetastasesBreastHead and neckAny neurologic eventEndocrineNot specified
Combined MET/SU: Observational Follow-up24143612110000005000130100
Combined RSG: Observational Follow-up25103222102110004411111100

Number of Participants With a Bone Fracture Event - Overall and by Gender: Main Study and Observational Follow-up Combined

The observational follow-up was designed to collect data concerning cancer and bone fractures in RECORD participants during a 4-year period after the end of the main RECORD study. At the end of the main study, all study medication was stopped. Participants were not provided with study medication in the observational follow-up; instead, anti-diabetic treatment was prescribed at the investigator's discretion. A bone fracture event is defined as one or more fractured bones occurring on the same date and that had the same Higher Level Group Term (HLGT) for fracture location, per participant. (NCT00379769)
Timeframe: From the beginning of the main study through the end of the observational follow-up (up to 11.4 years)

,
Interventionparticipants (Number)
Overall, n=2220, 2227Male, n=1142, 1152Female, n=1078, 1075
Combined MET/SU: Main Study and Observational Follow-up1516091
Combined RSG: Main Study and Observational Follow-up23882156

Number of Participants With a Bone Fracture Event - Overall and by Gender: Observational Follow-up

The observational follow-up was designed to collect data concerning cancer and bone fractures in RECORD participants during a 4-year period after the end of the main RECORD study. At the end of the main study, all study medication was stopped. Participants were not provided with study medication in the observational follow-up; instead, anti-diabetic treatment was prescribed at the investigator's discretion. A bone fracture event is defined as one or more fractured bones occurring on the same date and that had the same Higher Level Group Term (HLGT) for fracture location, per participant. (NCT00379769)
Timeframe: From the end of the RECORD study through the end of the observational follow-up (up to 4.0 years)

,
Interventionparticipants (Number)
Overall, n=1280, 1250Male, n=665, 635Female, n=615, 615
Combined MET/SU: Observational Follow-up371126
Combined RSG: Observational Follow-up642539

Number of Participants With a Bone Fracture Event Reported as the Indicated Serious Adverse Event (by Higher Level Group Term) or Death: Main Study + Observational Follow-up Combined

The OFU was designed to collect data concerning cancer and bone fractures in RECORD participants during a 4-year period after the end of the main RECORD study. At the end of the main study, all study medication was stopped. Participants were not provided with study medication in the OFU. A bone fracture event is defined as one or more fractured bones occurring on the same date and that had the same Higher Level Group Term (HLGT) for fracture location, per participant. An SAE is defined as any event that is fatal; life threatening; disabling/incapacitating; results in hospitalization (excluding elective surgery or routine clinical procedures); prolongs a hospital stay; is associated with a congenital abnormality; cancer; is associated with an overdose. In addition, any event that the investigator regards as serious or that would suggest any significant hazard, contraindication, side effect, or precaution that may be associated with the study procedures should be reported as an SAE. (NCT00379769)
Timeframe: From the beginning of the main study through the end of the observational follow-up (up to 11.4 years)

,
Interventionparticipants (Number)
Any eventUpper limbDistal lower limbFemur/hipSpinalPelvicOther
Combined MET/SU: Main Study and Observational Follow-up57171611934
Combined RSG: Main Study and Observational Follow-up81412415707

Number of Participants With a Bone Fracture Event Reported as the Indicated Serious Adverse Event (by Higher Level Group Term) or Death: Observational Follow-up

The OFU was designed to collect data concerning cancer and bone fractures in RECORD participants during a 4-year period after the end of the main RECORD study. At the end of the main study, all study medication was stopped. Participants were not provided with study medication in the OFU. A bone fracture event is defined as one or more fractured bones occurring on the same date and that had the same Higher Level Group Term (HLGT) for fracture location, per participant. An SAE is defined as any event that is fatal; life threatening; disabling/incapacitating; results in hospitalization (excluding elective surgery or routine clinical procedures); prolongs a hospital stay; is associated with a congenital abnormality; cancer; is associated with an overdose. In addition, any event that the investigator regards as serious or that would suggest any significant hazard, contraindication, side effect, or precaution that may be associated with the study procedures should be reported as an SAE. (NCT00379769)
Timeframe: From the end of the RECORD study through the end of the observational follow-up (up to 4.0 years)

,
Interventionparticipants (Number)
Any eventUpper limbDistal lower limbFemur/hipSpinalPelvicOther
Combined MET/SU: Observational Follow-up21584311
Combined RSG: Observational Follow-up351796202

Number of Participants With Addition of Third Oral Agent/Switch to Insulin

The number of participants with addition of a third oral agent or switch to insulin from randomised dual combination treatment were recorded. (NCT00379769)
Timeframe: Baseline through End of Study (up to 7.5 years)

,,,
Interventionparticipants (Number)
Participants with an eventFirst Event - Triple TherapyFirst Event - Insulin
MET in Addition to Background SU1716165
RSG in Addition to Background MET29525738
RSG in Addition to Background SU34429649
SU in Addition to Background MET1837176

Number of Participants With Bone Fracture Events of the Indicated Cause: Main Study + Observational Follow-up Combined

The observational follow-up was designed to collect data concerning cancer and bone fractures in RECORD participants during a 4-year period after the end of the main RECORD study. At the end of the main study, all study medication was stopped. Participants were not provided with study medication in the observational follow-up; instead, anti-diabetic treatment was prescribed at the investigator's discretion. A bone fracture event is defined as one or more fractured bones occurring on the same date and that had the same Higher Level Group Term (HLGT) for fracture location, per participant. (NCT00379769)
Timeframe: From the beginning of the main study through the end of the observational follow-up (up to 11.4 years)

,
Interventionparticipants (Number)
Any eventNon-traumatic eventTraumatic eventPathologicUnknownData unavailable
Combined MET/SU: Main Study and Observational Follow-up15155774193
Combined RSG: Main Study and Observational Follow-up2381131101209

Number of Participants With Bone Fracture Events of the Indicated Cause: Observational Follow-up

"The observational follow-up was designed to collect data concerning cancer and bone fractures in RECORD participants during a 4-year period after the end of the main RECORD study. At the end of the main study, all study medication was stopped. Participants were not provided with study medication in the observational follow-up; instead, anti-diabetic treatment was prescribed at the investigator's discretion. A bone fracture event is defined as one or more fractured bones occurring on the same date and that had the same Higher Level Group Term (HLGT) for fracture location, per participant. The indicated fracture outcome was pre-specified in the CRF and included Unknown as a category. Fracture events with missing outcome data were reported as Data unavailable." (NCT00379769)
Timeframe: From the end of the RECORD study through the end of the observational follow-up (up to 4.0 years)

,
Interventionparticipants (Number)
Any eventNon-traumatic event,Traumatic eventPathologicUnknownData unavailable
Combined MET/SU: Observational Follow-up371417241
Combined RSG: Observational Follow-up643624113

Number of Participants With Cardiovascular Events and All-cause Deaths

Composites of participants with first cardiovascular (CV) hospitalisations and CV death or all-cause death and individual first events of acute myocardial infarction (MI) , stroke, congestive heart failure (CHF), CV death, and all-cause death. (NCT00379769)
Timeframe: Baseline through End of Study (up to 7.5 years)

,
Interventionparticipants (Number)
CV death, acute MI, strokeCV death, acute MI, stroke, unstable anginaCV death, acute MI, stroke, unstable angina, CHFAll-cause death,acuteMI,stroke,unstable angina,CHFAcute MI (fatal or non-fatal)Stroke (fatal or non-fatal)CHF (fatal or non-fatal)Death from CV causesDeath (all cause) during CV follow-upDeath (all-cause) including survival status
Combined MET/SU16518420626856632971139157
Combined RSG15417120425164466160111136

Number of Participants With CV/Microvascular Events

The number of participants with first cardiovascular or microvascular events (renal, foot, eye) were recorded. (NCT00379769)
Timeframe: Baseline through End of Study (up to 7.5 years)

,
Interventionparticipants (Number)
Participants with a CV/Microvascular eventParticipants with any microvascular eventParticipants with any eye eventParticipants with any foot eventParticipants with any renal event
Combined MET/SU3857852280
Combined RSG3635942190

Number of Participants With Potentially High Morbidity Fracture Events and Non-high Morbidity Fracture Events, in Participants With Prior Hand/Upper Arm/Foot Fractures (H/UA/FF): Main Study + Observational Follow-up Combined

The observational follow-up was designed to collect data concerning cancer and bone fractures in RECORD participants during a 4-year period after the end of the main RECORD study. At the end of the main study, all study medication was stopped. Participants were not provided with study medication in the observational follow-up; instead, anti-diabetic treatment was prescribed at the investigator's discretion. A bone fracture event is defined as one or more fractured bones occurring on the same date and that had the same Higher Level Group Term (HLGT) for fracture location, per participant. The following bone fractures were grouped and were identified as potentially high morbidity bone fractures: hip, pelvis, upper leg, vertebral (lumbar spine, thoracic spine, cervical spine, spine - site unknown). (NCT00379769)
Timeframe: From the beginning of the main study through the end of the observational follow-up (up to 11.4 years)

,
Interventionparticipants (Number)
Any H/UA/FF event, overall, n=2220, 2227Any H/UA/FF event, male, n=1142, 1152Any H/UA/FF event, female, n=1078, 1075High morbidity fractures, overall, n=2220, 2227High morbidity fractures, male, n=1142, 1152High morbidity fractures, female, n=1078, 1075Non-high morbidity fractures, overall, n=2220, 222Non-high morbidity fractures, male, n=1142, 1152Non-high morbidity fractures, female, n=1078, 1075
Combined MET/SU: Main Study and Observational Follow-up461531101431
Combined RSG: Main Study and Observational Follow-up86285850515213

Number of Participants With Potentially High Morbidity Fractures: Main Study + Observational Follow-up Combined

The observational follow-up was designed to collect data concerning cancer and bone fractures in RECORD participants during a 4-year period after the end of the main RECORD study. At the end of the main study, all study medication was stopped. Participants were not provided with study medication in the observational follow-up; instead, anti-diabetic treatment was prescribed at the investigator's discretion. A bone fracture event is defined as one or more fractured bones occurring on the same date and that had the same Higher Level Group Term (HLGT) for fracture location, per participant. The following bone fractures were grouped and were identified as potentially high morbidity bone fractures: hip, pelvis, upper leg, vertebral (lumbar spine, thoracic spine, cervical spine, spine - site unknown). (NCT00379769)
Timeframe: From the beginning of the main study through the end of the observational follow-up (up to 11.4 years)

,
Interventionparticipants (Number)
Any event, overall, n=2220, 2227Any event, male, n=1142, 1152Any event, female, n=1078, 1075Hip, overall, n=2220, 2227Hip, male, n=1142, 1152Hip, female, n=1078, 1075Pelvis, overall, n=2220, 2227Pelvis, male, n=1142, 1152Pelvis, female, n=1078, 1075Upper leg, overall, n=2220, 2227Upper leg, male, n=1142, 1152Upper leg, female, n=1078, 1075Any vertebral event, overall, n=2220, 2227Any vertebral event, male, n=1142, 1152Any vertebral event, female, n=1078, 1075Lumbar spine, overall, n=2220, 2227Lumbar spine, male, n=1142, 1152Lumbar spine, female, n=1078, 1075Thoracic spine, overall, n=2220, 2227Thoracic spine, male, n=1142, 1152Thoracic spine, female, n=1078, 1075Cervical spine, overall, n=2220, 2227Cervical spine, male, n=1142, 1152Cervical spine, female, n=1078, 1075
Combined MET/SU: Main Study and Observational Follow-up3113187165416061385431844110
Combined RSG: Main Study and Observational Follow-up311021909000743166101055514101

Number of Participants With the Indicated Bone Fracture by Fracture Site: Main Study + Observational Follow-up Combined

The observational follow-up was designed to collect data concerning cancer and bone fractures in RECORD participants during a 4-year period after the end of the main RECORD study. At the end of the main study, all study medication was stopped. Participants were not provided with study medication in the observational follow-up; instead, anti-diabetic treatment was prescribed at the investigator's discretion. A bone fracture event is defined as one or more fractured bones occurring on the same date that had the same Higher Level Group Term (HLGT) for fracture location, per participant. (NCT00379769)
Timeframe: From the beginning of the main study through the end of the observational follow-up (up to 11.4 years)

,
Interventionparticipants (Number)
Any event, overall; n=2220, 2227Any event, male; n=1142, 1152Any event, female; n=1078, 1075Upper limb, any event, overall; n=2220, 2227Upper limb, any event, male; n=1142, 1152Upper limb, any event, female; n=1078, 1075Distal lower limb, any event, overall; n=2220, 222Distal lower limb, any event, male; n=1142, 1152Distal lower limb, any event, female; n=1078, 1075Femur/hip, any event, overall; n=2220, 2227Femur/hip, any event, male; n=1142, 1152Femur/hip, any event, female; n=1078, 1075Spinal, any event, overall; n=2220, 2227Spinal, any event, male; n=1142, 1152Spinal, any event, female; n=1078, 1075Pelvic, any event, overall; n=2220, 2227Pelvic, any event, male; n=1142, 1152Pelvic, any event, female; n=1078, 1075Unclassified, any event, overall; n=2220, 2227Unclassified, any event, male; n=1142, 1152Unclassified, any event, female; n=1078, 1075Other, any event, overall; n=2220, 2227Other, any event, male; n=1142, 1152Other, any event, female; n=1078, 1075
Combined MET/SU: Main Study and Observational Follow-up1516091702248401426131121495541000261610
Combined RSG: Main Study and Observational Follow-up2388215611632848831571641218711000110311813

Number of Participants With the Indicated Bone Fracture by Fracture Site: Observational Follow-up

The observational follow-up was designed to collect data concerning cancer and bone fractures in RECORD participants during a 4-year period after the end of the main RECORD study. At the end of the main study, all study medication was stopped. Participants were not provided with study medication in the observational follow-up; instead, anti-diabetic treatment was prescribed at the investigator's discretion. A bone fracture event is defined as one or more fractured bones occurring on the same date that had the same Higher Level Group Term (HLGT) for fracture location, per participant. (NCT00379769)
Timeframe: From the end of the RECORD study through the end of the observational follow-up (up to 4.0 years)

,
Interventionparticipants (Number)
Any event, overall; n=1280, 1250Any event, male; n=665, 635Any event, female; n=615, 615Upper limb, any event, overall; n=1280, 1250Upper limb, any event, male; n=665, 635Upper limb, any event, female; n=615, 615Distal lower limb, any event, overall; n=1280,1250Distal lower limb, any event, male; n=665, 635Distal lower limb, any event, female; n=615, 615Femur/hip, any event, overall; n=1280, 1250Femur/hip, any event, male; n=665, 635Femur/hip, any event, female; n=615, 615Spinal, any event, overall; n=1280, 1250Spinal, any event, male; n=665, 635Spinal, any event, female; n=615, 615Pelvic, any event, overall; n=1280, 1250Pelvic, any event, male; n=665, 635Pelvic, any event, female; n=615, 615Unclassified, any event, overall; n=1280, 1250Unclassified, any event, male; n=665, 635Unclassified, any event, female; n=615, 615Other, any event, overall; n=1280, 1250Other, any event, male; n=665, 635Other, any event, female; n=615, 615
Combined MET/SU: Observational Follow-up371126153121349505541110000110
Combined RSG: Observational Follow-up6425393310231899615413000110642

Number of Participants With the Indicated Serious Adverse Event: Observational Follow-up

The observational follow-up was designed to collect data concerning cancer and bone fractures in RECORD participants during a 4-year period after the end of the main RECORD study. At the end of the main study, all study medication was stopped. Participants were not provided with study medication in the observational follow-up; instead, anti-diabetic treatment was prescribed at the investigator's discretion. An SAE is defined as any event that is fatal; life threatening; disabling/incapacitating; results in hospitalization (excluding elective surgery or routine clinical procedures); prolongs a hospital stay; is associated with a congenital abnormality; cancer; is associated with an overdose. In addition, any event that the investigator regards as serious or that would suggest any significant hazard, contraindication, side effect, or precaution that may be associated with the study procedures should be reported as an SAE. (NCT00379769)
Timeframe: From the end of the RECORD study through the end of the observational follow-up (up to 4.0 years)

,
Interventionparticipants (Number)
Any eventAnkle fractureProstate cancerLung neoplasm malignantBreast cancerBasal cell carcinomaPancreatic carcinomaColon cancerHumerus fractureUpper limb fractureMalignant melanomaUterine cancerGastric cancerWrist fractureHip fractureRadius fractureForearm fractureHepatic neoplasm malignantRectal cancerRenal cancerFoot fractureRenal cell carcinomaFemur fractureFemoral neck fractureLumbar vertebral fractureMetastases to boneMetastases to liverBladder cancerFallMetastases to central nervous systemRib fractureSquamous cell carcinomaAcute myocardial infarctionBrain neoplasmGastric neoplasmMetastases to lungPatella fractureDeathAbdominal painAcute myeloid leukaemiaAcute respiratory failureAnaemiaBenign salivary gland neoplasmBiliary colicBiliary neoplasmBone neoplasm malignantBronchial carcinomaCardiac failure acuteChest painChronic lymphocytic leukaemiaColon neoplasmContusionDrowningDysplasiaEndometrial cancer stage ILeukaemiaLower limb fractureLung squamous cell carcinoma stage unspecifiedLymphomaMalignant neoplasm of pleuraMetastases to skinMetastases to testicleMetastatic renal cell carcinomaOesophageal carcinomaOsteoarthritisPancreatic necrosisRectal cancer stage IISpinal fractureT-cell lymphomaUrinary tract infectionUterine leiomyosarcomaBiliary cancer metastaticCervix carcinomaChronic obstructive pulmonary diseaseComminuted fractureCraniocerebral injuryGastrointestinal neoplasmHepatic lesionJoint dislocationLaryngeal cancerLip neoplasm malignant stage unspecifiedLung neoplasmMetastases to lymph nodesMetastasisMusculoskeletal chest painMyocardial infarctionNon-Hodgkin's lymphomaPubis fracturePulmonary embolismRectal cancer recurrentRectal neoplasmSkin cancerSkin ulcerSmall cell lung cancer stage unspecifiedSternal fractureSubdural haemorrhageSudden deathThoracic vertebral fractureThyroid cancerVulval cancer
Combined MET/SU: Observational Follow-up76314633611230011222230122220000011111200000000000000000000000000000111011111111111111111111111111111
Combined RSG: Observational Follow-up99674244155324433222213211112222211111011111111111111111111111111111111100000000000000000000000000000

Number of Participants With the Indicated Type of Malignant Neoplasms/Cancer Events Reported as an SAE or Death by Location (Including Location of Special Interest): Main Study + Observational Follow-up Combined

The observational follow-up (OFU) was designed to collect data concerning cancer and bone fractures in RECORD participants during a 4-year period after the end of the main RECORD study. At the end of the main study, all study medication was stopped. Participants were not provided with study medication in the OFU. The neoplasms/cancer events of bladder, breast, colon, liver, pancreatic, prostate cancer, and melanoma were pre-specified as cancers of interest for the OFU. An SAE is defined as any event that is fatal; life threatening; disabling/incapacitating; results in hospitalization (excluding elective surgery or routine clinical procedures); prolongs a hospital stay; is associated with a congenital abnormality; cancer; is associated with an overdose. In addition, any event that the investigator regards as serious or that would suggest any significant hazard, contraindication, side effect, or precaution that may be associated with the study procedures should be reported as an SAE. (NCT00379769)
Timeframe: From the beginning of the main study through the end of the observational follow-up (up to 11.4 years)

,
Interventionparticipants (Number)
Any genitourinaryProstateRenalUterineBladderVaginal/vulvarOvarianAny gastrointestinalColon/rectal cancerColonGastricPancreaticLiverGall bladder/biliaryGastrointestinal; not specifiedAny hematologicLungSkin (non-melanomatous)Skin (melanomatous)MetastasesBreastHead and neckNeurologicEndocrineNot specifiedOther
Combined MET/SU: Main Study and Observational Follow-up5722916514623021516551615134182373613
Combined RSG: Main Study and Observational Follow-up572212118154822141354401219196121243300

Number of Participants With the Indicated Type of Malignant Neoplasms/Cancer Events Reported as an SAE or Death by Location (Including Location of Special Interest): Observational Follow-up

The observational follow-up (OFU) was designed to collect data concerning cancer and bone fractures in RECORD participants during a 4-year period after the end of the main RECORD study. At the end of the main study, all study medication was stopped. Participants were not provided with study medication in the OFU. The neoplasms/cancer events of bladder, breast, colon, liver, pancreatic, prostate cancer, and melanoma were pre-specified as cancers of interest for the OFU. An SAE is defined as any event that is fatal; life threatening; disabling/incapacitating; results in hospitalization (excluding elective surgery or routine clinical procedures); prolongs a hospital stay; is associated with a congenital abnormality; cancer; is associated with an overdose. In addition, any event that the investigator regards as serious or that would suggest any significant hazard, contraindication, side effect, or precaution that may be associated with the study procedures should be reported as an SAE. (NCT00379769)
Timeframe: From the end of the RECORD study through the end of the observational follow-up (up to 4.0 years)

,
Interventionparticipants (Number)
Any genitourinaryProstateRenalUterineBladderVaginal/vulvarOvarianAny gastrointestinalColon/rectal cancerColonGastricPancreaticLiverGall bladder/biliaryGastrointestinal; not specifiedAny hematologicLungSkin (non-melanomatous)Skin (melanomatous)MetastasesBreastHead and neckNeurologicEndocrineNot specifiedOther
Combined MET/SU: Observational Follow-up8124010191171321116526711100
Combined RSG: Observational Follow-up1875420017525421066633221000

Number of Participants With the Indicated Type of Neoplasm/Cancer Event Reported as a Serious Adverse Event (SAE) or Death: Main Study + Observational Follow-up Combined

The observational follow-up was designed to collect data concerning cancer and bone fractures in RECORD participants during a 4-year period after the end of the main RECORD study. At the end of the main study, all study medication was stopped. Participants were not provided with study medication in the observational follow-up; instead, anti-diabetic treatment was prescribed at the investigator's discretion. An SAE is defined as any event that is fatal; life threatening; disabling/incapacitating; results in hospitalization (excluding elective surgery or routine clinical procedures); prolongs a hospital stay; is associated with a congenital abnormality; cancer; is associated with an overdose. In addition, any event that the investigator regards as serious or that would suggest any significant hazard, contraindication, side effect, or precaution that may be associated with the study procedures should be reported as an SAE. (NCT00379769)
Timeframe: From the beginning of the main study through the end of the observational follow-up (up to 11.4 years)

,
Interventionparticipants (Number)
All neoplasms/cancer (N/C) (benign/malignant)Malignant (Mal.) N/CMal. N/C; excluding non-melanomatous skin cancers
Combined MET/SU: Main Study and Observational Follow-up215195186
Combined RSG: Main Study and Observational Follow-up196179164

Number of Participants With the Indicated Type of Neoplasm/Cancer Event Reported as a Serious Adverse Event (SAE) or Death: Observational Follow-up

The observational follow-up was designed to collect data concerning cancer and bone fractures in RECORD participants during a 4-year period after the end of the main RECORD study. At the end of the main study, all study medication was stopped. Participants were not provided with study medication in the observational follow-up; instead, anti-diabetic treatment was prescribed at the investigator's discretion. An SAE is defined as any event that is fatal; life threatening; disabling/incapacitating; results in hospitalization (excluding elective surgery or routine clinical procedures); prolongs a hospital stay; is associated with a congenital abnormality; cancer; is associated with an overdose. In addition, any event that the investigator regards as serious or that would suggest any significant hazard, contraindication, side effect, or precaution that may be associated with the study procedures should be reported as an SAE. (NCT00379769)
Timeframe: From the end of the RECORD study through the end of the observational follow-up (up to 4.0 years)

,
Interventionparticipants (Number)
All neoplasms/cancer (N/C) (benign/malignant)Malignant (Mal.) N/CMal. N/C; excluding non-melanomatous skin cancers
Combined MET/SU: Observational Follow-up515146
Combined RSG: Observational Follow-up605955

Total Number of Cardiovascular Hospitalisations and Cardiovascular Deaths

The total number of events for individual components of cardiovascular (CV) hospitalisations and cardiovascular deaths were recorded. MI, myocardial infarction. (NCT00379769)
Timeframe: Baseline through End of Study (up to 7.5 years)

,
InterventionNumber of events (Number)
CV deathsDeath due to acute MIDeath due to heart failureSudden deathDeath due to acute vascular eventsOther CV mortalityDeath of presumed CV causeCardiovascular hospitalisationHospitalisation for acute MIHospitalisation for unstable anginaHospitalisation for congestive heart failureHospitalisation for strokeHospitalisation for transient ischaemic attackHospitalisation for invasive CV procedureHospitalisation for amputation of extremitiesOther CV hospitalisations
Combined MET/SU711021210433490572836671011623153
Combined RSG60710816284836628695110996154

The Change in Levels of High Sensitivity C-reactive Protein From Baseline to 16 Weeks in the Sitagliptin and Gliclazide Arms.

High sensitivity C-reactive protein (range 0 - no maximum) (NCT01991197)
Timeframe: 16 weeks

Interventionµg/ml (Median)
Sitagliptin0
Gliclazide8.4

The Change in Levels of Serum Glucose From Baseline to 16 Weeks in the Sitagliptin and Gliclazide Arms.

The change in glucose from baseline to 16 weeks (NCT01991197)
Timeframe: 16 weeks

Interventionmmol/L (Median)
Sitagliptin-0.2
Gliclazide-0.1

The Change in Levels of Systolic Blood Pressure From Baseline to 16 Weeks in the Sitagliptin and Gliclazide Arms.

The change in systolic blood pressure from baseline to 16 weeks measured in kg (NCT01991197)
Timeframe: 16 weeks

InterventionmmHg (Median)
Sitagliptin4
Gliclazide-9

The Change in Levels of Total Cholesterol From Baseline to 16 Weeks in the Sitagliptin and Gliclazide Arms.

The change in total cholesterol from baseline to 16 weeks (NCT01991197)
Timeframe: 16 weeks

Interventionmmol/L (Median)
Sitagliptin0.1
Gliclazide-0.1

The Change in PASI From Baseline to 32 Weeks in Psoriasis Patients With Type 2 Diabetes Treated With Sitagliptin Compared to Patients Treated With Gliclazide.

Psoriasis area and severity index 0-72, higher score worse outcome (NCT01991197)
Timeframe: baseline and 32 weeks

Interventionscore on a scale (Median)
Sitagliptin3
Gliclazide1.8

The Change in the Psoriasis Area and Severity Index (PASI) From Baseline to 16 Weeks in Psoriasis Patients With Type 2 Diabetes Treated With Sitagliptin Compared to Patients Treated With Gliclazide.

Psoriasis area and severity index (0-72), higher scores worse outcome (NCT01991197)
Timeframe: 16 weeks

Interventionscore on a scale (Median)
Sitagliptin9.5
Gliclazide9.4

The Change in Weight From Baseline to 16 Weeks in the Sitagliptin and Gliclazide Arms.

The change in weight from baseline to 16 weeks measured in kg (NCT01991197)
Timeframe: 16 weeks

Interventionkg (Median)
Sitagliptin-0.5
Gliclazide-0.6

The Effect of Treatment With Sitagliptin and With Gliclazide From Baseline to 16 Weeks on the Change in Dipeptidyl Peptidase-4 Levels in the Skin (in a Sub-group of Participants Willing to Undergo Skin Biopsies).

Dipeptidyl peptidase-4 levels levels in skin (0-no maximum) (NCT01991197)
Timeframe: 16 weeks

InterventiondCt (Median)
Gliclazide-1.12
Sitagliptin0

The Effect of Treatment With Sitagliptin and With Gliclazide From Baseline to 16 Weeks on the Change in Interleukin-17 Levels in the Skin (in a Sub-group of Participants Willing to Undergo Skin Biopsies).

Interleukin 17 levels in skin (0-no maximum) (NCT01991197)
Timeframe: 16 weeks

InterventiondCt (Median)
Sitagliptin3.41
Gliclazide2.09

The Effects of Treatment With Sitagliptin and Treatment With Gliclazide From Baseline to 16 Weeks on Serum Levels Interleukin-17.

"Secondary outcomes:~The change in serum concentrations of the cytokine interleukin-17 (IL-17) Range: 0-no maximum" (NCT01991197)
Timeframe: 16 weeks

Interventionpg/ml (Median)
Sitagliptin0
Gliclazide0

The Effects of Treatment With Sitagliptin and Treatment With Gliclazide From Baseline to 16 Weeks on Serum Levels Interleukin-23.

"Secondary outcomes:~The change in serum concentrations of the cytokine interleukin-23 (IL-23) Range: 0-no maximum" (NCT01991197)
Timeframe: 16 weeks

Interventionpg/ml (Median)
Sitagliptin0
Gliclazide0

The Effects of Treatment With Sitagliptin and Treatment With Gliclazide on the Change in Serum Leptin From Baseline to 16 Weeks.

"Secondary outcomes:~The change in serum concentrations of the adipokine leptin Range: 0-no maximum" (NCT01991197)
Timeframe: 16 weeks

Interventionpg/ml (Median)
Sitagliptin-0.07
Gliclazide0.43

The Effects of Treatment With Sitagliptin and Treatment With Gliclazide on the Serum Cytokine Tumour Necrosis Factor Alpha.

"Secondary outcomes:~The change in serum concentrations of the cytokines tumour necrosis factor alpha (TNFα) Range: 0-no maximum" (NCT01991197)
Timeframe: 16 weeks

Interventionpg/ml (Median)
Sitagliptin0
Gliclazide0

The Number of Patricipants in the Sitagliptin and Gliclazide Arms With Adverse Events at 32 Weeks.

"Dosage: Sitagliptin: 100mg daily, or 50mg daily for participants with moderate kidney disease Gliclazide: 80-320 mg daily.~Secondary outcomes: the number participants with adverse events." (NCT01991197)
Timeframe: 32 weeks

InterventionParticipants (Count of Participants)
Sitagliptin6
Gliclazide10

The Change in Quality of Life Scores From Baseline to 16 Weeks in the Sitagliptin and Gliclazide Arms.

"Dermatology life quality index (a skin related quality of life measure) (0-10), higher score worse outcome EQ-5D Euroqol 5 item quality of life index comprising 5 dimensions mobility, self-care, usual activities, pain, anxiety. An index can be derived from these 5 dimensions by conversion with a table of scores. The maximum score of 1 indicates the best health state and minimum score indicating the worst health outcome -0.594.~HADS Hospital anxiety and depression scale 0-16 for anxiety and 0-16 for depression, higher score worse outcome HAQ-8 Stanford 8 item disability scale. Scoring is from 0 (without any difficulty) to 3 (unable to do). The 8 scores from the 8 sections are summed and divided by 8. The result is the disability index (range 0-3 with 25 possible values). A" (NCT01991197)
Timeframe: 16 weeks

,
Interventionscore on a scale (Median)
DLQIHAQ-8HADS AnxietyHADS DepressionEQ-5D
Gliclazide-1.00.000-0.2
Sitagliptin0.00.0-100

The Effects of Treatment With Sitagliptin and Treatment With Gliclazide on Other Efficacy Endpoints.

"Secondary outcomes:~d. number or participants who acheived a greater than 50% reduction in PASI from baseline (PASI-50); e. number of participants who achieved PASI-75 and PASI-90." (NCT01991197)
Timeframe: 16 weeks

,
InterventionParticipants (Count of Participants)
PASI 50PASI 75PASI 90
Gliclazide100
Sitagliptin100

Changes From Baseline in Grip Strength Via a Dynamometer During and Following Exposure to Metformin.

Grip strength over time. (NCT03772964)
Timeframe: Day 0 (baseline), 90, and 120 (30 days post metformin exposure)

,,,
InterventionmmHg (Mean)
0 days90 days, compared to 0 days120 days, compared to 0 days
1000mg Exposure28.9-0.41.1
1500mg Exposure25.7-.2.3
500mg Exposure28.2-5.3.1
Placebo25.7-.3-.6

Changes From Baseline in Short Physical Performance Battery (SPPB) During and Following Exposure to Metformin.

The SPPB is a group of measures that combines the results of the gait speed, chair stand and balance tests. The minimum is zero (worse performance) and the maximum is 12 (best performance). (NCT03772964)
Timeframe: Day 0 (baseline), 90, and 120 (30 days post metformin exposure)

,,,
InterventionUnits on a scale (Mean)
0d90d, change from 0d120d, change from 0d
1000mg Exposure10.80.40.2
1500mg Exposure11.10.40.3
500mg Exposure11.2-0.30
Placebo10.61.00.5

Measure the Rate of Clotting of Peripheral Blood With Whole Blood Aggregometry in Response to Collagen.

Aggregometry area under the curve with the Y-axis being % aggregometry and the X-axis time in minutes. (NCT03772964)
Timeframe: Day 0 (baseline), 30, 60, 90, and 120 (30 days post metformin exposure)

,,,
Interventionarbitrary units*mins (Mean)
0 days30 day change from day 060 days change from day 090 days change from day 0120 days change from day 0
1000mg Exposure678.9-23.52.41.0
1500mg Exposure196-166.7-139.8-222.5-196.7
500mg Exposure56.3-34.7-28.31.6-49.2
Placebo83.3-29.6-49.4-66.6-47.6

Quantify the Bacterial Population Profile of the Microbiome Via Stool Samples.

"Bacterial communities using 16S rRNA sequencing in relationship to metformin dosing over time. Species richness or diversity in the sample is measured by Choa1 metric. Chao1 is an estimate of how many species are present in an ecosystem. In general, having more species is considered to be healthier and these values typically range from 100-200 for fecal samples. The Chao1 index over numerous samples across time are explored to understand treatment effects." (NCT03772964)
Timeframe: Day 0 (baseline), 30, 60, 90, and 120 (30 days post metformin exposure)

,,,
InterventionIndex (Mean)
Day 0Day 30Day 60Day 90Day 120
1000mg Exposure107.6130.7137.9135142.2
1500mg Exposure128.1128.1128.6138.2144.2
500mg Exposure136.5139.9121.4137.8134
Placebo141.5144.75134.3152159.2

Effects of Pioglitazone on 24h Blood Pressure Control

24 hour blood pressure measurements were performed after each treatment/diet phase (NCT01090752)
Timeframe: march 2009

InterventionmmHg (Mean)
Pioglitazone Low Salt/High Salt128
Placebo Low Salt/High Salt129

Effects of Pioglitazone on Renal Hemodynamics

At the end of each treatment diet phase, renal clearances were performed for the determination of GFR and RBF (NCT01090752)
Timeframe: 2008

Interventionml/min/1.73m2 (Mean)
Pioglitazone Low Salt/High Salt68.0
Placebo Low Salt/High Salt62.4

Effects of Pioglitazone on Sodium and Lithium Clearances

At the end of each treatment and diet phase, 24 urine collections were collected for the determination of sodium and lithium clearances (NCT01090752)
Timeframe: 2007

Interventionml/min (Mean)
Pioglitazone Low Salt/High Salt1.05
Placebo Low Salt/High Salt1.18

Change in Fasting Glucose From Baseline to 16 Weeks

fasting blood glucose (NCT00816907)
Timeframe: 16 weeks

Interventionmg/dL (Least Squares Mean)
Placebo-1.6
Metformin-2.3

Change in Fasting Insulin From Baseline to 16 Weeks

Fasting insulin (NCT00816907)
Timeframe: 16 weeks

InterventionmU/L (Mean)
Placebo5.5
Metformin1.6

Change in HDL Cholesterol From Baseline to 16 Weeks

high-density lipoprotein (NCT00816907)
Timeframe: 16 weeks

Interventionmg/dL (Least Squares Mean)
Placebo-0.4
Metformin-0.6

Change in Hemoglobin A1c From Baseline to 16 Weeks

glycosylated hemoglobin (NCT00816907)
Timeframe: 16 weeks

Interventionpercent (Least Squares Mean)
Placebo0.01
Metformin-0.06

Change in LDL Cholesterol From Baseline to 16 Weeks

low-density lipoprotein (NCT00816907)
Timeframe: 16 weeks

Interventionmg/dL (Least Squares Mean)
Placebo-2.0
Metformin-7.1

Change in Total Cholesterol From Baseline to 16 Weeks

Total cholesterol (NCT00816907)
Timeframe: 16 weeks

Interventionmg/dL (Mean)
Placebo0.2
Metformin-8.9

Change in Triglycerides From Baseline to 16 Weeks

serum triglycerides (NCT00816907)
Timeframe: 16 weeks

Interventionmg/dL (Least Squares Mean)
Placebo13.2
Metformin-7.0

Mean Difference in Body Weight Change Between Participants Assigned to Metformin and Participants Assigned to Placebo

Mean difference in body weight change between participants assigned to metformin and participants assigned to placebo from baseline to last study visit (up to 16 weeks) (NCT00816907)
Timeframe: Measured at the last study visit

Interventionkilograms (Mean)
Placebo-1.0
Metformin-3.0

Change in Body Weight

Change in body weight following 30 weeks of therapy (i.e., body weight at week 30 minus body weight at baseline) (NCT00765817)
Timeframe: baseline and 30 weeks

Interventionkg (Least Squares Mean)
Exenatide Arm-1.78
Placebo Arm0.96

Change in Daily Insulin Dose

Change in daily insulin dose following 30 weeks of therapy (i.e., daily insulin dose at week 30 minus daily insulin dose at baseline) (NCT00765817)
Timeframe: baseline and 30 weeks

Interventioninsulin units (U) (Least Squares Mean)
Exenatide Arm13.19
Placebo Arm19.71

Change in Daily Insulin Dose (on a Per Body Weight Basis)

Change in daily insulin dose per kilogram (kg) following 30 weeks of therapy (i.e., daily insulin dose per kg at week 30 minus daily insulin dose per kg at baseline) (NCT00765817)
Timeframe: baseline and 30 weeks

Interventioninsulin units per kg (U/kg) (Least Squares Mean)
Exenatide Arm0.15
Placebo Arm0.20

Change in Diastolic Blood Pressure (DBP)

Change in DBP following 30 weeks of therapy (i.e., DBP at week 30 minus DBP at baseline) (NCT00765817)
Timeframe: baseline and 30 weeks

InterventionmmHg (Least Squares Mean)
Exenatide Arm-1.73
Placebo Arm1.69

Change in Fasting Serum Glucose

Change in fasting serum glucose following 30 weeks of therapy (i.e., fasting serum glucose at week 30 minus fasting serum glucose at baseline) (NCT00765817)
Timeframe: baseline and 30 weeks

Interventionmmol/L (Least Squares Mean)
Exenatide Arm-1.28
Placebo Arm-0.87

Change in Glycosylated Hemoglobin (HbA1c)

Change in HbA1c from baseline following 30 weeks of therapy (i.e., HbA1c at week 30 minus HbA1c at baseline). Unit of measure is percent of hemoglobin that is glycosylated. (NCT00765817)
Timeframe: baseline and 30 weeks

Interventionpercentage of hemoglobin (Least Squares Mean)
Exenatide Arm-1.71
Placebo Arm-1.00

Change in High Density Lipoprotein (HDL) Cholesterol

Change in HDL cholesterol following 30 weeks of therapy (i.e., HDL cholesterol at week 30 minus HDL cholesterol at baseline) (NCT00765817)
Timeframe: baseline and 30 weeks

Interventionmmol/L (Least Squares Mean)
Exenatide Arm0.01
Placebo Arm0.00

Change in Low Density Lipoprotein (LDL) Cholesterol

Change in LDL cholesterol following 30 weeks of therapy (i.e., LDL cholesterol at week 30 minus LDL cholesterol at baseline) (NCT00765817)
Timeframe: baseline and 30 weeks

Interventionmmol/L (Least Squares Mean)
Exenatide Arm-0.19
Placebo Arm-0.00

Change in Systolic Blood Pressure (SBP)

Change in SBP following 30 weeks of therapy (i.e., SBP at week 30 minus SBP at baseline) (NCT00765817)
Timeframe: baseline and 30 weeks

InterventionmmHg (Least Squares Mean)
Exenatide Arm-2.74
Placebo Arm1.71

Change in Total Cholesterol

Change in total cholesterol following 30 weeks of therapy (i.e., total cholesterol at week 30 minus total cholesterol at baseline) (NCT00765817)
Timeframe: baseline and 30 weeks

Interventionmmol/L (Least Squares Mean)
Exenatide Arm-0.16
Placebo Arm-0.02

Change in Triglycerides

Change in triglycerides following 30 weeks of therapy (i.e., triglycerides at week 30 minus triglycerides at baseline) (NCT00765817)
Timeframe: baseline and 30 weeks

Interventionmmol/L (Least Squares Mean)
Exenatide Arm-0.02
Placebo Arm-0.03

Change in Waist Circumference

Change in waist circumference following 30 weeks of therapy (i.e., waist circumference at week 30 minus waist circumference at baseline) (NCT00765817)
Timeframe: baseline and 30 weeks

Interventioncm (Least Squares Mean)
Exenatide Arm-1.08
Placebo Arm-0.25

Minor Hypoglycemia Rate Per Year

Number of minor hypoglycemia events experienced per subject per year. Minor hypoglycemia was defined as any time a subject felt he or she was experiencing a sign or symptom associated with hypoglycemia that was either self-treated by the subject or resolved on its own and had a concurrent finger stick blood glucose <3.0 mmol/L (54 mg/dL). (NCT00765817)
Timeframe: baseline and weeks 2, 4, 6, 8, 10, 14, 18, 22, 26, and 30

Interventionevents per subject per year (Mean)
Exenatide Arm1.61
Placebo Arm1.55

Percentage of Patients Achieving HbA1c <=6.5%

Percentage of patients in each arm who had HbA1c >6.5% at baseline and had HbA1c <=6.5% at week 30 (percentage = [number of subjects with HbA1c <=6.5% at week 30 divided by number of subjects with HbA1c >6.5% at baseline] * 100%). (NCT00765817)
Timeframe: baseline and 30 weeks

Interventionpercentage (Number)
Exenatide Arm42.0
Placebo Arm13.3

Percentage of Patients Achieving HbA1c <=7%

Percentage of patients in each arm who had HbA1c >7% at baseline and had HbA1c <=7% at week 30 (percentage = [number of subjects with HbA1c <=7% at week 30 divided by number of subjects with HbA1c >7% at baseline] * 100%). (NCT00765817)
Timeframe: baseline and 30 weeks

Interventionpercentage (Number)
Exenatide Arm58.3
Placebo Arm31.1

Percentage of Subjects Experiencing Minor Hypoglycemia

Percentage of subjects in each arm experiencing at least one episode of minor hypoglycemia at any point during the study. Minor hypoglycemia was defined as any time a subject felt he or she was experiencing a sign or symptom associated with hypoglycemia that was either self-treated by the subject or resolved on its own and had a concurrent finger stick blood glucose <3.0 mmol/L (54 mg/dL). (NCT00765817)
Timeframe: baseline and weeks 2, 4, 6, 8, 10, 14, 18, 22, 26, and 30

Interventionpercentage (Number)
Exenatide Arm24.8
Placebo Arm28.7

Change in 7-point Self-monitored Blood Glucose (SMBG) Profile

Change in 7-point (pre-breakfast, 2 hour post-breakfast, pre-lunch, 2 hour post-lunch, pre-dinner, 2 hour post-dinner, 0300 hours) SMBG profile from baseline to week 30 (change = blood glucose value at week 30 minus blood glucose value at baseline) (NCT00765817)
Timeframe: baseline and 30 weeks

,
Interventionmmol/L (Least Squares Mean)
Pre-breakfast: baselinePre-breakfast: change at week 302 hour post-breakfast: baseline2 hour post-breakfast: change at week 30Pre-lunch: baselinePre-lunch: change at week 302 hour post-lunch: baseline2 hour post-lunch: change at week 30Pre-dinner: baselinePre-dinner: change at week 302 hour post-dinner: baseline2 hour post-dinner: change at week 300300: baseline0300: change at week 30
Exenatide Arm7.89-1.5810.89-3.568.95-2.2311.35-2.749.85-2.2512.03-3.878.95-2.27
Placebo Arm8.27-1.4811.82-1.729.77-1.1511.70-1.389.99-1.3311.86-1.349.20-1.48

Change in Body Fat by Bod Pod

Change in body fat mass measured by air displacement plethysmography (kg) (NCT00005669)
Timeframe: 6 months

Interventionkg (Mean)
Metformin Plus Weight Reduction Counseling-1.51
Placebo Plus Weight Reduction Counseling1.81

Change in Body Fat by DEXA

Change in body fat mass by Dual Energy X-Ray Absorptiometry (kg) (NCT00005669)
Timeframe: 6 months

Interventionkg (Mean)
Metformin Plus Weight Reduction Counseling0.48
Placebo Plus Weight Reduction Counseling1.88

Change in Body Weight

Change in body weight (kg) (NCT00005669)
Timeframe: 6 months

Interventionkg (Mean)
Metformin Plus Weight Reduction Counseling1.47
Placebo Plus Weight Reduction Counseling4.85

Change in Body Weight as Determined by BMI

Change in body weight as determined by body mass index (kg/m2) (NCT00005669)
Timeframe: 6 months

Interventionkg/m2 (Mean)
Metformin Plus Weight Reduction Counseling-0.78
Placebo Plus Weight Reduction Counseling0.32

Changes in Body Weight as Determined by Body Mass Index-standard Deviation Score (BMI-SDS).

Change in Body Mass Index standard deviation score (BMI-SDS) determined using tables created by the CDC in 2000. BMI-SDS is a unitless transformation of the body mass index (measured in kg divided by the squared height in meters) using the L M S method. Possible values range from -3 to +3. See http://www.cdc.gov/growthcharts/percentile_data_files.htm for details. (NCT00005669)
Timeframe: 6 months

InterventionUnits on a scale (Mean)
Metformin Plus Weight Reduction Counseling-0.11
Placebo Plus Weight Reduction Counseling-0.07

Beta-cell Function 4 Weeks After Cessation of Therapy

Treatment effect on beta-cell function as measured by the ratio of Week 56 arginine-stimulated insulin secretion during a hyperglycemic clamp(specifically, the incremental AUC of insulin with respect to basal value over a 10 min period [i.e., clamp time 290 min to 300 min]) to that at baseline (i.e., the ratio is calculated as arginine-stimulated insulin secretion at week 56 divided by arginine-stimulated insulin secretion at baseline [week -2]). (NCT00097500)
Timeframe: Baseline (week -2) and 56 weeks

Interventionratio (Least Squares Mean)
Exenatide Arm1.02
Insulin Glargine Arm1.08

Beta-cell Function After 52 Weeks of Therapy

Treatment effect on beta-cell function as measured by the ratio of Week 52 arginine-stimulated insulin secretion during a hyperglycemic clamp(specifically, the incremental AUC of insulin with respect to basal value over a 10 min period [i.e., clamp time 290 min to 300 min]) to that at baseline (i.e., the ratio is calculated as arginine-stimulated insulin secretion at week 52 divided by arginine-stimulated insulin secretion at baseline [week -2]). (NCT00097500)
Timeframe: Baseline (week -2) and 52 weeks

Interventionratio (Least Squares Mean)
Exenatide Arm2.89
Insulin Glargine Arm1.15

Change in Body Weight

Change in body weight from week 0 to week 52 (i.e., body weight at week 52 minus body weight at week 0). (NCT00097500)
Timeframe: 0 weeks and 52 weeks

Interventionkg (Least Squares Mean)
Exenatide Arm-3.80
Insulin Glargine Arm0.75

Change in Fasting Plasma Glucose

Change in fasting plasma glucose from week 0 to week 52 (i.e., fasting plasma glucose at week 52 minus fasting plasma glucose at week 0). (NCT00097500)
Timeframe: 0 weeks and 52 weeks

Interventionmmol/L (Least Squares Mean)
Exenatide Arm-1.53
Insulin Glargine Arm-3.10

Change in Glycosylated Hemoglobin (HbA1c)

Change in HbA1c from week 0 to week 52 (i.e., HbA1c at week 52 minus HbA1c at week 0). (NCT00097500)
Timeframe: Week 0 and week 52

Interventionpercent (Least Squares Mean)
Exenatide Arm-0.97
Insulin Glargine Arm-0.87

Change in First Phase C-peptide Release

Ratio of first phase C-peptide response to glucose at 52 weeks (end of on-drug period) and 56 weeks (during off-drug period) compared to first phase C-peptide response to glucose at baseline (i.e., C-peptide response to glucose at week 52 or week 56 divided by C-peptide response to glucose at baseline [week -2]). C-peptide is measured as a surrogate marker of insulin secretion. First phase C-peptide/insulin release is measured during the first ten minutes of glucose infusion during a hyperglycemic clamp procedure. (NCT00097500)
Timeframe: baseline (week -2), 52 weeks, and 56 weeks

,
Interventionratio (Least Squares Mean)
52 weeks56 weeks
Exenatide Arm1.720.95
Insulin Glargine Arm1.131.06

Change in Second Phase C-peptide Release

Ratio of second phase C-peptide response to glucose at 52 weeks (end of on-drug period) and 56 weeks (during off-drug period) compared to second phase C-peptide response to glucose at baseline (i.e., C-peptide response to glucose at week 52 or week 56 divided by C-peptide response to glucose at baseline [week -2]). C-peptide is measured as a surrogate marker of insulin secretion. Second phase C-peptide/insulin release is measured from time=10 minutes to time=80 minutes of glucose infusion during a hyperglycemic clamp procedure. (NCT00097500)
Timeframe: baseline (-2 weeks), 52 weeks, and 56 weeks

,
Interventionratio (Least Squares Mean)
52 weeks56 weeks
Exenatide Arm2.881.00
Insulin Glargine Arm1.011.08

M-value at Baseline, Week 52 and Week 56

M-value at baseline (week -2), week 52 (end of on-drug period), and week 56 (during off-drug period). Insulin sensitivity was assessed during the euglycemic/hyperglycemic clamp test at baseline (week -2), week 52, and week 56. Insulin-mediated glucose uptake (M-value) was calculated as the mean glucose requirement during the 90-120 minute interval of the clamp. (NCT00097500)
Timeframe: baseline (week -2), 52 weeks, and 56 weeks

,
Interventionmg/min/kg (Mean)
baseline (week -2)week 52week 56
Exenatide Arm2.243.183.19
Insulin Glargine Arm2.793.852.81

Seven Point Self Monitored Blood Glucose (SMBG) Measurements

SMBG measured at 7 time points (before and after breakfast, before and after lunch, before and after dinner, at bedtime). (NCT00097500)
Timeframe: 0 weeks and 52 weeks

,
Interventionmmol/L (Mean)
Pre-breakfast measurement (week 0)Pre-breakfast measurement (week 52)2-hour post-breakfast measurement (week 0)2-hour post-breakfast measurement (week 52)Pre-lunch measurement (week 0)Pre-lunch measurement (week 52)2-hour post-lunch measurement (week 0)2-hour post-lunch measurement (week 52)Pre-dinner measurement (week 0)Pre-dinner measurement (week 52)2-hour post-dinner measurement (week 0)2-hour post-dinner measurement (week 52)Bedtime measurement (week 0)Bedtime measurement (week 52)
Exenatide Arm8.927.2711.006.988.146.529.907.978.387.5310.426.989.767.61
Insulin Glargine Arm8.385.6311.177.538.546.2410.528.158.076.9810.268.819.858.03

Hepatic Fat

The effect of exenatide and pioglitazone on liver fat content after one year of treatment in patients with type 2 diabetes. (NCT01432405)
Timeframe: one year

Interventionpercent of liver fat (Mean)
Pioglitazone and Exenatide4.7
Pioglitazone6.5

Plasma Adipocytokines

the effect of the intervention on plasma adiponectin levels. (NCT01432405)
Timeframe: one year

Interventionmicrogram per ml (Mean)
Pioglitazone and Exenatide23.2
Pioglitazone15.8

Adjusted Mean Change From Baseline in Fasting Plasma Glucose (FPG) at Week 24 (Last Observation Carried Forward [LOCF])

Secondary endpoints were tested using sequential testing procedure and are presented in hierarchical order. Fasting plasma glucose was measured as milligrams per deciliter(mg/dL) by a central laboratory. Baseline was defined as the last assessment prior to the start date and time of the first dose of the double-blind study medication. In cases where time of the first dose or time of the assessment was not available, baseline was defined as the last assessment on or prior to the date of the first dose of the double-blind study medication. FPG measurements were obtained during the qualification and lead-in periods and on Day 1 and Weeks 1, 2, 3, 4, 6, 8, 12, 16, 20, and 24 in the double-blind period. (NCT00643851)
Timeframe: From Baseline to Week 24

Interventionmg/dL (Mean)
Dapagliflozin 5 mg + Metformin XR-61.0
Dapagliflozin 5 mg-42.0
Metformin XR-33.6

Adjusted Mean Change From Baseline in Hemoglobin A1C (HbA1c) at Week 24 (Last Observation Carried Forward [LOCF])

HbA1c was measured as percent of hemoglobin by a central laboratory. Data after rescue medication was excluded from this analysis. Baseline was defined as the last assessment prior to the start date and time of the first dose of the double-blind study medication. In cases where time of the first dose or time of the assessment was not available, baseline was defined as the last assessment on or prior to the date of the first dose of the double-blind study medication. HbA1c measurements were obtained during the qualification and lead-in periods and on Day 1 and Weeks 4, 8, 12, 16, 20, and 24 in the double- blind period. (NCT00643851)
Timeframe: From Baseline to Week 24

Intervention% of hemoglobin (Mean)
Dapagliflozin 5 mg + Metformin XR-2.05
Dapagliflozin 5 mg-1.19
Metformin XR-1.35

Adjusted Mean Change From Baseline in Hemoglobin A1C (HbA1c) in Subjects With Baseline HbA1c ≥ 9% at Week 24 (Last Observation Carried Forward [LOCF])

HbA1c was measured as percent of hemoglobin by a central laboratory. Data after rescue medication was excluded from this analysis. Baseline was defined as the last assessment prior to the start date and time of the first dose of the double-blind study medication. In cases where time of the first dose or time of the assessment was not available, baseline was defined as the last assessment on or prior to the date of the first dose of the double-blind study medication. HbA1c measurements were obtained during the qualification and lead-in periods and on Day 1 and Weeks 4, 8, 12, 16, 20, and 24 in the double-blind period. (NCT00643851)
Timeframe: From Baseline to Week 24

Intervention% of hemoglobin (Mean)
Dapagliflozin 5 mg + Metformin XR-3.01
Dapagliflozin 5 mg-1.67
Metformin XR-1.82

Adjusted Mean Change From Baseline in Total Body Weight (kg) at Week 24 (Last Observation Carried Forward [LOCF])

Secondary endpoints were tested using sequential testing procedure and are presented in hierarchical order. Adjusted mean change from baseline in total body weight at Week 24 (or the last postbaseline measurement prior to Week 24 if no Week 24 assessment was available was determined. Data after rescue medication was excluded from this analysis. Baseline was defined as the last assessment prior to the start date and time of the first dose of the double-blind study medication. In cases where time of the first dose or time of the assessment was not available, baseline was defined as the last assessment on or prior to the date of the first dose of the double-blind study medication. Body weight measurements were obtained during the qualification and lead-in periods and on Day 1 and Weeks 1, 2, 3, 4, 6, 8, 12, 16, 20, and 24 of the double-blind period. (NCT00643851)
Timeframe: From Baseline to Week 24

Interventionkg (Mean)
Dapagliflozin 5 mg + Metformin XR-2.66
Dapagliflozin 5 mg-2.61
Metformin XR-1.29

Adjusted Mean Change From Baseline in Total Body Weight (kg) in Subjects With Baseline Body Mass Index (BMI) ≥ 27 kg/m^2 at Week 24 (Last Observation Carried Forward [LOCF])

Secondary endpoints were tested using sequential testing procedure and are presented in hierarchical order. Adjusted mean change from baseline in total body weight at Week 24 (or the last postbaseline measurement prior to Week 24 if no Week 24 assessment was available was determined. Data after rescue medication was excluded from this analysis. Baseline was defined as the last assessment prior to the start date and time of the first dose of the double-blind study medication. In cases where time of the first dose or time of the assessment was not available, baseline was defined as the last assessment on or prior to the date of the first dose of the double-blind study medication. Body weight measurements were obtained during the qualification and lead-in periods and on Day 1 and Weeks 1, 2, 3, 4, 6, 8, 12, 16, 20, and 24 of the double-blind period. (NCT00643851)
Timeframe: From Baseline to Week 24

Interventionkg (Mean)
Dapagliflozin 5 mg + Metformin XR-3.04
Dapagliflozin 5 mg-2.88
Metformin XR-1.47

Percentage of Participants Achieving a Therapeutic Glycemic Response (Hemoglobin A1c [HbA1C]) <7.0% at Week 24 (Last Observation Carried Forward [LOCF])

Secondary endpoints were tested using sequential testing procedure and are presented in hierarchical order. Percent adjusted for baseline HbA1c. Therapeutic glycemic response is defined as HbA1c <7.0%. Data after rescue medication was excluded from this analysis. HbA1c was measured as a percent of hemoglobin. Mean and standard error for percentage of participants estimated by modified logistic regression model. (NCT00643851)
Timeframe: From Baseline to Week 24

InterventionPercentage of participants (Mean)
Dapagliflozin 5 mg + Metformin XR52.4
Dapagliflozin 5 mg22.5
Metformin XR34.6

Change in Body Weight From Baseline to Study Endpoint

(NCT00751114)
Timeframe: baseline (week 0), study endpoint: visit 14 (week 24) or visit 12 (week 16) or visit 11 (week 12) or visit 8 (week 6) depending on last available value

Interventionkg (Least Squares Mean)
Insulin Glargine0.44
Sitagliptin-1.08

HbA1c Response Rate: Percentage of Patients Who Reach the Target of HbA1c < 6.5% at Study Endpoint

(NCT00751114)
Timeframe: study endpoint: visit 14 (week 24) or visit 11 (week 12) if value not available at visit 14

Interventionpercentage of participants (Number)
Insulin Glargine40.2
Sitagliptin16.9

HbA1c Response Rate: Percentage of Patients Who Reach the Target of HbA1c < 7% at Study Endpoint

(NCT00751114)
Timeframe: study endpoint: visit 14 (week 24) or visit 11 (week 12) if value not available at visit 14

Interventionpercentage of participants (Number)
Insulin Glargine67.9
Sitagliptin41.9

HbA1c: Change From Baseline to Study Endpoint

Change in HbA1c from baseline to study endpoint defined as the last available HbA1c value measured during the 24-week treatment period. (NCT00751114)
Timeframe: baseline (week 0), study endpoint: visit 14 (week 24) or visit 11 (week 12) if value not available at visit 14

Interventionpercent (Least Squares Mean)
Insulin Glargine-1.72
Sitagliptin-1.13

Number of Patients With at Least One Episode of Severe Symptomatic Hypoglycemia

Severe symptomatic hypoglycemia was defined as an event with clinical symptoms which required assistance of another person and with either a Plasma Glucose level < 36 mg/dL (2 mmol/L) or with a prompt recovery after oral carbohydrate, intravenous glucose, or glucagon administration (NCT00751114)
Timeframe: During the treatment phase (24 weeks) plus 7 days after last dose

Interventionparticipants (Number)
Insulin Glargine3
Sitagliptin1

Number of Patients With at Least One Episode of Symptomatic Hypoglycemia

Symptomatic hypoglycemia was defined as an event with clinical symptoms that were considered to result from hypoglycemia confirmed or not by a plasma glucose measurement <= 70mg/dL [3.9 mmol/L] (NCT00751114)
Timeframe: During the treatment phase (24 weeks) plus 7 days after last dose

Interventionparticipants (Number)
Insulin Glargine108
Sitagliptin35

Self-monitored Fasting Plasma Glucose (SMFPG) Mean : Change From Baseline to Study Endpoint

"SMFPG mean = mean of the fasting plasma glucose values recorded on the 6 consecutive days before the visit (at least 3 values needed).~Study endpoint was defined as the last available SMFPG mean value collected on-treatment.~Change= study endpoint - baseline" (NCT00751114)
Timeframe: baseline (week 0), study endpoint: visit 14 (week 24) or visit 12 (week 16) or visit 11 (week 12) or visit 8 (week 6) depending on last available value

Interventionmg/dL (Least Squares Mean)
Insulin Glargine-60.52
Sitagliptin-19.35

7-point Plasma Glucose Profile: Change From Baseline to Study Endpoint

"7-point plasma glucose recorded before and after breakfast, before and after lunch, before and after dinner and at bedtime.~Change = study endpoint - baseline." (NCT00751114)
Timeframe: baseline (week 0), study endpoint: visit 14 (week 24) or visit 11 (week 12) if value not available at visit 14

,
Interventionmg/dL (Least Squares Mean)
Before breakfast (N ig = 203 & N s = 226)After breakfast (N ig = 202 & N s = 220)Before lunch (N ig = 201 & N s = 223)After lunch (N ig = 202 & N s = 226)Before dinner (N ig = 199 & N s = 223)After dinner (N ig = 196 & N s = 220)At bedtime (N ig = 177 & N s = 210)
Insulin Glargine-59.90-66.25-48.00-45.54-40.68-45.88-45.58
Sitagliptin-20.39-36.41-19.82-26.10-25.07-33.78-31.16

Insulin Dose in the Insulin Glargine Group

Daily dose at the face-to-face visits. (NCT00751114)
Timeframe: visit 4 (week 2), visit 8 (week 6), visit 11 (week 12), visit 12 (week 16), visit 14 (week 24), first dose received defined as first available value, study endpoint defined as last available value

Interventionunit per kg body weight (Mean)
First dose received N=236Visit 4 (week 2) N=230Visit 8 (week 6) N=222Visit 11 (week 12) N=219Visit 12 (week 16) N=214Visit 14 (week 24) N=220Study endpoint N=237
Insulin Glargine0.190.270.380.450.480.500.49

Lipid Profile: Change From Baseline to Study Endpoint

(NCT00751114)
Timeframe: baseline (week 0), study endpoint: visit 14 (week 24) or visit 11 (week 12) if value not available at visit 14

,
Interventionmg/dL (Least Squares Mean)
Change in Total CholesterolChange in LDL CholesterolChange in HDL CholesterolChange in Triglycerides
Insulin Glargine-7.94-3.680.13-34.07
Sitagliptin-1.54-0.190.570.31

Mean Change From Baseline in Adiponectin at Week 26.

Calculated as an estimate of the mean change from baseline in Adiponectin at Week 26. (NCT00700817)
Timeframe: Week 0, Week 26

Interventionmcg/mL (Least Squares Mean)
Lira 1.2 mg -> Lira 1.2 mg -> Lira 1.2 mg1.69
Lira 1.8 mg -> Lira 1.8 mg -> Lira 1.8 mg1.51
Sita -> Sita1.35

Mean Change From Baseline in Apolipoprotein B at Week 26

Calculated as an estimate of the change from baseline in apolipoprotein B (ApoB) at Week 26. (NCT00700817)
Timeframe: Week 0, Week 26

Interventiong/L (Least Squares Mean)
Lira 1.2 mg -> Lira 1.2 mg -> Lira 1.2 mg-0.06
Lira 1.8 mg -> Lira 1.8 mg -> Lira 1.8 mg-0.07
Sita -> Sita-0.05

Mean Change From Baseline in Apolipoprotein B at Week 52

Calculated as an estimate of the change from baseline in apolipoprotein B (ApoB) at Week 52. (NCT00700817)
Timeframe: Week 0, Week 52

Interventiong/L (Least Squares Mean)
Lira 1.2 mg -> Lira 1.2 mg -> Lira 1.2 mg-0.03
Lira 1.8 mg -> Lira 1.8 mg -> Lira 1.8 mg-0.03
Sita -> Sita-0.03

Mean Change From Baseline in Beta-cell Function at Week 26

"Calculated as an estimate of the mean change from baseline in beta-cell function at Week 26.~Derived from fasting plasma glucose (FPG) and fasting insulin using the homeostatic model assessment (HOMA) method with the assumption that normal-weight subjects aged under 35 years have a 100% beta-cell function (HOMA-B)." (NCT00700817)
Timeframe: Week 0, Week 26

Interventionpercentage point (Least Squares Mean)
Lira 1.2 mg -> Lira 1.2 mg -> Lira 1.2 mg27.23
Lira 1.8 mg -> Lira 1.8 mg -> Lira 1.8 mg28.70
Sita -> Sita4.18

Mean Change From Baseline in Beta-cell Function at Week 52

"Calculated as an estimate of the mean change from baseline in beta-cell function at Week 52.~Derived from fasting plasma glucose (FPG) and fasting insulin using the homeostatic model assessment (HOMA) method with the assumption that normal-weight subjects aged under 35 years have a 100% beta-cell function (HOMA-B)." (NCT00700817)
Timeframe: Week 0, Week 52

Interventionpercentage point (Least Squares Mean)
Lira 1.2 mg -> Lira 1.2 mg -> Lira 1.2 mg22.58
Lira 1.8 mg -> Lira 1.8 mg -> Lira 1.8 mg25.76
Sita -> Sita3.98

Mean Change From Baseline in Body Weight at Week 26

Calculated as an estimate of the mean change from baseline in body weight at Week 26. (NCT00700817)
Timeframe: Week 0, Week 26

Interventionkg (Least Squares Mean)
Lira 1.2 mg -> Lira 1.2 mg -> Lira 1.2 mg-2.86
Lira 1.8 mg -> Lira 1.8 mg -> Lira 1.8 mg-3.38
Sita -> Sita-0.96

Mean Change From Baseline in Body Weight at Week 52

Calculated as an estimate of the mean change from baseline in body weight at Week 52. (NCT00700817)
Timeframe: Week 0, Week 52

Interventionkg (Least Squares Mean)
Lira 1.2 mg -> Lira 1.2 mg -> Lira 1.2 mg-2.78
Lira 1.8 mg -> Lira 1.8 mg -> Lira 1.8 mg-3.68
Sita -> Sita-1.16

Mean Change From Baseline in Diastolic Blood Pressure (DBP) at Week 26

Calculated as an estimate of the mean change from baseline in diastolic blood pressure (DBP) at Week 26. (NCT00700817)
Timeframe: Week 0, Week 26

InterventionmmHg (Least Squares Mean)
Lira 1.2 mg -> Lira 1.2 mg -> Lira 1.2 mg-0.71
Lira 1.8 mg -> Lira 1.8 mg -> Lira 1.8 mg0.07
Sita -> Sita-1.78

Mean Change From Baseline in Diastolic Blood Pressure (DBP) at Week 52

Calculated as an estimate of the mean change from baseline in diastolic blood pressure (DBP) at Week 52. (NCT00700817)
Timeframe: Week 0, Week 52

InterventionmmHg (Least Squares Mean)
Lira 1.2 mg -> Lira 1.2 mg -> Lira 1.2 mg-0.53
Lira 1.8 mg -> Lira 1.8 mg -> Lira 1.8 mg-0.87
Sita -> Sita-1.47

Mean Change From Baseline in Fasting Plasma Glucose (FPG) at Week 26

Calculated as an estimate of the mean change from baseline in fasting plasma glucose (FPG) at Week 26. (NCT00700817)
Timeframe: Week 0, Week 26

Interventionmmol/L (Least Squares Mean)
Lira 1.2 mg -> Lira 1.2 mg -> Lira 1.2 mg-1.87
Lira 1.8 mg -> Lira 1.8 mg -> Lira 1.8 mg-2.14
Sita -> Sita-0.83

Mean Change From Baseline in Fasting Plasma Glucose (FPG) at Week 52

Calculated as an estimate of the mean change from baseline in fasting plasma glucose (FPG) at Week 52. (NCT00700817)
Timeframe: Week 0, Week 52

Interventionmmol/L (Least Squares Mean)
Lira 1.2 mg -> Lira 1.2 mg -> Lira 1.2 mg-1.71
Lira 1.8 mg -> Lira 1.8 mg -> Lira 1.8 mg-2.04
Sita -> Sita-0.59

Mean Change From Baseline in Fasting Plasma Glucose (FPG) at Week 78

Calculated as an estimate of the mean change in fasting plasma glucose (FPG) from baseline to Week 78. (NCT00700817)
Timeframe: Week 0, Week 78

Interventionmmol/L (Least Squares Mean)
Lira 1.2 mg -> Lira 1.2 mg -> Lira 1.2 mg-1.30
Lira 1.8 mg -> Lira 1.8 mg -> Lira 1.8 mg-1.65

Mean Change From Baseline in Free Fatty Acids (FFA) at Week 26

Calculated as an estimate of the change from baseline in free fatty acids (FFA) at Week 26. (NCT00700817)
Timeframe: Week 0, Week 26

Interventionmmol/L (Least Squares Mean)
Lira 1.2 mg -> Lira 1.2 mg -> Lira 1.2 mg-0.03
Lira 1.8 mg -> Lira 1.8 mg -> Lira 1.8 mg-0.07
Sita -> Sita-0.05

Mean Change From Baseline in Free Fatty Acids (FFA) at Week 52

Calculated as an estimate of the change from baseline in free fatty acids (FFA) at Week 52. (NCT00700817)
Timeframe: Week 0, Week 52

Interventionmmol/L (Least Squares Mean)
Lira 1.2 mg -> Lira 1.2 mg -> Lira 1.2 mg-0.07
Lira 1.8 mg -> Lira 1.8 mg -> Lira 1.8 mg-0.10
Sita -> Sita-0.06

Mean Change From Baseline in Glycosylated Haemoglobin A1c (HbA1c) at Week 26

Calculated as an estimate of the mean change from baseline in glycosylated haemoglobin A1c (HbA1c) at Week 26. (NCT00700817)
Timeframe: Week 0, Week 26

InterventionPercentage point of total HbA1c (Least Squares Mean)
Lira 1.2 mg -> Lira 1.2 mg -> Lira 1.2 mg-1.24
Lira 1.8 mg -> Lira 1.8 mg -> Lira 1.8 mg-1.5
Sita -> Sita-0.9

Mean Change From Baseline in Glycosylated Haemoglobin A1c (HbA1c) at Week 52

Calculated as an estimate of the mean change from baseline in glycosylated haemoglobin A1c (HbA1c) at Week 52. (NCT00700817)
Timeframe: Week 0, Week 52

InterventionPercentage point of total HbA1c (Least Squares Mean)
Lira 1.2 mg -> Lira 1.2 mg -> Lira 1.2 mg-1.29
Lira 1.8 mg -> Lira 1.8 mg -> Lira 1.8 mg-1.51
Sita -> Sita-0.88

Mean Change From Baseline in Glycosylated Haemoglobin A1c (HbA1c) at Week 78

Calculated as an estimate of the mean change from baseline in glycosylated haemoglobin A1c (HbA1c) at Week 78. (NCT00700817)
Timeframe: Week 0, Week 78

InterventionPercentage point of total HbA1c (Least Squares Mean)
Lira 1.2 mg -> Lira 1.2 mg -> Lira 1.2 mg-0.94
Lira 1.8 mg -> Lira 1.8 mg -> Lira 1.8 mg-1.28

Mean Change From Baseline in High-density Lipoprotein-cholesterol (HDL-C) at Week 26

Calculated as an estimate of the mean change from baseline in high-density lipoprotein-cholesterol (HDL-C) at Week 26. (NCT00700817)
Timeframe: Week 0, Week 26

Interventionmmol/L (Least Squares Mean)
Lira 1.2 mg -> Lira 1.2 mg -> Lira 1.2 mg0.00
Lira 1.8 mg -> Lira 1.8 mg -> Lira 1.8 mg0.00
Sita -> Sita0.00

Mean Change From Baseline in High-density Lipoprotein-cholesterol (HDL-C) at Week 52

Calculated as an estimate of the mean change from baseline in high-density lipoprotein-cholesterol (HDL-C) at Week 52. (NCT00700817)
Timeframe: Week 0, Week 52

Interventionmmol/L (Least Squares Mean)
Lira 1.2 mg -> Lira 1.2 mg -> Lira 1.2 mg0.01
Lira 1.8 mg -> Lira 1.8 mg -> Lira 1.8 mg0.02
Sita -> Sita0.01

Mean Change From Baseline in Highly Sensitive C-reactive Protein (hsCRP) at Week 26

Calculated as an estimate of the mean change from baseline in highly sensitive C-reactive protein (hsCRP) at week 26. (NCT00700817)
Timeframe: Week 0, Week 26

Interventionmg/L (Least Squares Mean)
Lira 1.2 mg -> Lira 1.2 mg -> Lira 1.2 mg-1.02
Lira 1.8 mg -> Lira 1.8 mg -> Lira 1.8 mg-0.99
Sita -> Sita-0.66

Mean Change From Baseline in Interleukin-6 (IL-6) at Week 26.

Calculated as an estimate of the mean change from baseline in interleukin-6 (IL-6) at Week 26. (NCT00700817)
Timeframe: Week 0, Week 26

Interventionpg/mL (Least Squares Mean)
Lira 1.2 mg -> Lira 1.2 mg -> Lira 1.2 mg-1.70
Lira 1.8 mg -> Lira 1.8 mg -> Lira 1.8 mg1.71
Sita -> Sita0.91

Mean Change From Baseline in Low-density Lipoprotein-cholesterol (LDL-C) at Week 26

Calculated as an estimate of the mean change in low-density lipoprotein-cholesterol (LDL-C) at Week 26. (NCT00700817)
Timeframe: Week 0, Week 26

Interventionmmol/L (Least Squares Mean)
Lira 1.2 mg -> Lira 1.2 mg -> Lira 1.2 mg0.08
Lira 1.8 mg -> Lira 1.8 mg -> Lira 1.8 mg0.05
Sita -> Sita0.13

Mean Change From Baseline in Low-density Lipoprotein-cholesterol (LDL-C) at Week 52

Calculated as an estimate of the mean change in low-density lipoprotein-cholesterol (LDL-C) at Week 52. (NCT00700817)
Timeframe: Week 0, Week 52

Interventionmmol/L (Least Squares Mean)
Lira 1.2 mg -> Lira 1.2 mg -> Lira 1.2 mg0.09
Lira 1.8 mg -> Lira 1.8 mg -> Lira 1.8 mg0.09
Sita -> Sita0.17

Mean Change From Baseline in N-terminal Pro B-type Natriuretic Peptide (NT-proBNP) at Week 26.

Calculated as an estimate of the mean change from baseline in N-terminal pro B-type Natriuretic Peptide (NT-proBNP) at Week 26. (NCT00700817)
Timeframe: Week 0, Week 26

Interventionpmol/L (Least Squares Mean)
Lira 1.2 mg -> Lira 1.2 mg -> Lira 1.2 mg5.19
Lira 1.8 mg -> Lira 1.8 mg -> Lira 1.8 mg3.74
Sita -> Sita3.71

Mean Change From Baseline in Overall Treatment Satisfaction (OTS) at Week 26

The Overall Treatment Satisfaction is a sum of 6 items from the Diabetes Treatment Satisfaction Questionnaire, which is a self-assessment of treatment satisfaction. The scale of each sub-item goes from 0 (lowest satisfaction) to 6 (highest satisfaction) and the overall scale of OTS therefore goes from 0 to 36. (NCT00700817)
Timeframe: Week 0, Week 26

Interventionscores on a scale (Least Squares Mean)
Lira 1.2 mg -> Lira 1.2 mg -> Lira 1.2 mg3.51
Lira 1.8 mg -> Lira 1.8 mg -> Lira 1.8 mg4.35
Sita -> Sita2.96

Mean Change From Baseline in Overall Treatment Satisfaction (OTS) at Week 52

The Overall Treatment Satisfaction is a sum of 6 items from the Diabetes Treatment Satisfaction Questionnaire, which is a self-assessment of treatment satisfaction. The scale of each sub-item goes from 0 (lowest satisfaction) to 6 (highest satisfaction) and the overall scale of OTS therefore goes from 0 to 36. (NCT00700817)
Timeframe: Week 0, Week 52

Interventionscores on a scale (Least Squares Mean)
Lira 1.2 mg -> Lira 1.2 mg -> Lira 1.2 mg3.32
Lira 1.8 mg -> Lira 1.8 mg -> Lira 1.8 mg4.31
Sita -> Sita2.96

Mean Change From Baseline in Plasminogen Activator Inhibitor-1 (PAI-1) at Week 26.

Calculated as an estimate of the mean change from baseline in plasminogen activator inhibitor-1 (PAI-1) at Week 26. (NCT00700817)
Timeframe: Week 0, Week 26

InterventionU/L (Least Squares Mean)
Lira 1.2 mg -> Lira 1.2 mg -> Lira 1.2 mg-833
Lira 1.8 mg -> Lira 1.8 mg -> Lira 1.8 mg-561
Sita -> Sita586

Mean Change From Baseline in Pulse at Week 26

Calculated as an estimate of the mean change from baseline in pulse at Week 26. (NCT00700817)
Timeframe: Week 0, Week 26

Interventionbeats/minute (Least Squares Mean)
Lira 1.2 mg -> Lira 1.2 mg -> Lira 1.2 mg2.32
Lira 1.8 mg -> Lira 1.8 mg -> Lira 1.8 mg3.94
Sita -> Sita-0.64

Mean Change From Baseline in Pulse at Week 52

Calculated as an estimate of the mean change from baseline in pulse at Week 52. (NCT00700817)
Timeframe: Week 0, Week 52

InterventionmmHg (Least Squares Mean)
Lira 1.2 mg -> Lira 1.2 mg -> Lira 1.2 mg1.72
Lira 1.8 mg -> Lira 1.8 mg -> Lira 1.8 mg3.09
Sita -> Sita0.09

Mean Change From Baseline in Systolic Blood Pressure (SBP) at Week 26

Calculated as an estimate of the mean change from baseline in Systolic Blood Pressure (SBP) at Week 26 (NCT00700817)
Timeframe: Week 0, Week 26

InterventionmmHg (Least Squares Mean)
Lira 1.2 mg -> Lira 1.2 mg -> Lira 1.2 mg-0.55
Lira 1.8 mg -> Lira 1.8 mg -> Lira 1.8 mg-0.72
Sita -> Sita-0.94

Mean Change From Baseline in Systolic Blood Pressure (SBP) at Week 52

Calculated as an estimate of the mean change from baseline in systolic blood pressure (SBP) at Week 52. (NCT00700817)
Timeframe: Week 0, Week 52

InterventionmmHg (Least Squares Mean)
Lira 1.2 mg -> Lira 1.2 mg -> Lira 1.2 mg-0.37
Lira 1.8 mg -> Lira 1.8 mg -> Lira 1.8 mg-2.55
Sita -> Sita-1.03

Mean Change From Baseline in Total Cholesterol at Week 26

Calculated as an estimate of the mean change from baseline in total cholesterol at Week 26. (NCT00700817)
Timeframe: Week 0, Week 26

Interventionmmol/L (Least Squares Mean)
Lira 1.2 mg -> Lira 1.2 mg -> Lira 1.2 mg-0.03
Lira 1.8 mg -> Lira 1.8 mg -> Lira 1.8 mg-0.17
Sita -> Sita-0.02

Mean Change From Baseline in Total Cholesterol at Week 52

Calculated as an estimate of the mean change from baseline in total cholesterol at Week 52. (NCT00700817)
Timeframe: Week 0, Week 52

Interventionmmol/L (Least Squares Mean)
Lira 1.2 mg -> Lira 1.2 mg -> Lira 1.2 mg-0.01
Lira 1.8 mg -> Lira 1.8 mg -> Lira 1.8 mg-0.09
Sita -> Sita0.03

Mean Change From Baseline in Triglycerides (TG) at Week 26

Calculated as an estimate of the change from baseline in triglycerides (TG) at Week 26. (NCT00700817)
Timeframe: Week 0, Week 26

Interventionmmol/L (Least Squares Mean)
Lira 1.2 mg -> Lira 1.2 mg -> Lira 1.2 mg-0.19
Lira 1.8 mg -> Lira 1.8 mg -> Lira 1.8 mg-0.43
Sita -> Sita-0.40

Mean Change From Baseline in Triglycerides (TG) at Week 52

Calculated as an estimate of the change from baseline in triglycerides (TG) at Week 52. (NCT00700817)
Timeframe: Week 0, Week 52

Interventionmmol/L (Least Squares Mean)
Lira 1.2 mg -> Lira 1.2 mg -> Lira 1.2 mg-0.10
Lira 1.8 mg -> Lira 1.8 mg -> Lira 1.8 mg-0.32
Sita -> Sita-0.23

Mean Change From Baseline in Tumour Necrosis Factor Alpha (TNF-alpha) at Week 26.

Calculated as an estimate of the mean change from baseline in Tumour Necrosis Factor Alpha (TNF-alpha) at Week 26. (NCT00700817)
Timeframe: Week 0, Week 26

Interventionpg/mL (Least Squares Mean)
Lira 1.2 mg -> Lira 1.2 mg -> Lira 1.2 mg-0.55
Lira 1.8 mg -> Lira 1.8 mg -> Lira 1.8 mg-0.74
Sita -> Sita-0.53

Mean Change From Baseline in Very Low-density Lipoprotein-cholesterol (VLDL-C) at Week 26

Calculated as an estimate of the change from baseline in very low-density lipoprotein-cholesterol (VLDL-C) at Week 26. (NCT00700817)
Timeframe: Week 0, Week 26

Interventionmmol/L (Least Squares Mean)
Lira 1.2 mg -> Lira 1.2 mg -> Lira 1.2 mg-0.11
Lira 1.8 mg -> Lira 1.8 mg -> Lira 1.8 mg-0.20
Sita -> Sita-0.15

Mean Change From Baseline in Very Low-density Lipoprotein-cholesterol (VLDL-C) at Week 52

Calculated as an estimate of the change from baseline in very low-density lipoprotein-cholesterol (VLDL-C) at Week 52. (NCT00700817)
Timeframe: Week 0, Week 52

Interventionmmol/L (Least Squares Mean)
Lira 1.2 mg -> Lira 1.2 mg -> Lira 1.2 mg-0.11
Lira 1.8 mg -> Lira 1.8 mg -> Lira 1.8 mg-0.19
Sita -> Sita-0.15

Mean Change From Baseline in Von Willebrand Factor (vWf) at Week 26.

Calculated as an estimate of the mean change from baseline in von Willebrand Factor (vWf) at Week 26. vWf is a blood glycoprotein involved in haemostasis. (NCT00700817)
Timeframe: Week 0, Week 26

Interventionpercentage point (Least Squares Mean)
Lira 1.2 mg -> Lira 1.2 mg -> Lira 1.2 mg-1.73
Lira 1.8 mg -> Lira 1.8 mg -> Lira 1.8 mg-4.34
Sita -> Sita-1.8

Mean Change From Baseline in Waist Circumference at Week 26.

Calculated as an estimate of the mean change from baseline in Waist Circumference at Week 26 (NCT00700817)
Timeframe: Week 0, Week 26

Interventioncm (Least Squares Mean)
Lira 1.2 mg -> Lira 1.2 mg -> Lira 1.2 mg-2.69
Lira 1.8 mg -> Lira 1.8 mg -> Lira 1.8 mg-2.63
Sita -> Sita-1.12

Mean Change From Baseline in Waist Circumference at Week 52

Calculated as an estimate of the mean change from baseline in Waist Circumference at Week 52. (NCT00700817)
Timeframe: Week 0, Week 52

Interventionparticipants (Least Squares Mean)
Lira 1.2 mg -> Lira 1.2 mg -> Lira 1.2 mg-2.36
Lira 1.8 mg -> Lira 1.8 mg -> Lira 1.8 mg-3.02
Sita -> Sita-1.23

Mean Change From Baseline in Waist to Hip Ratio at Week 26.

Calculated as an estimate of the mean change from baseline in Waist to Hip Ratio at Week 26. The measure is assessed as the circumference of the waist divided by the circumference of the hip. (NCT00700817)
Timeframe: Week 0, Week 26

Interventioncm/cm (Least Squares Mean)
Lira 1.2 mg -> Lira 1.2 mg -> Lira 1.2 mg-0.01
Lira 1.8 mg -> Lira 1.8 mg -> Lira 1.8 mg-0.01
Sita -> Sita-0.00

Mean Change From Baseline in Waist to Hip Ratio at Week 52

Calculated as an estimate of the mean change from baseline in Waist to Hip Ratio at Week 52. The measure is assessed as the circumference of the waist divided by the circumference of the hip. (NCT00700817)
Timeframe: Week 0, Week 52

Interventioncm/cm (Least Squares Mean)
Lira 1.2 mg -> Lira 1.2 mg -> Lira 1.2 mg-0.00
Lira 1.8 mg -> Lira 1.8 mg -> Lira 1.8 mg-0.01
Sita -> Sita-0.00

Mean Change in Apolipoprotein B From Week 52 to Week 78

Mean change in apolipoprotein B (ApoB) from Week 52 to Week 78. (NCT00700817)
Timeframe: Week 52, Week 78

Interventionmmol/L (Mean)
Sita -> Sita -> Lira 1.2 mg0.23
Sita -> Sita -> Lira 1.8 mg0.17

Mean Change in Beta-cell Function From Week 52 to Week 78

Mean change in beta-cell function from Week 52 to Week 78. Derived from fasting plasma glucose (FPG) and fasting insulin using the homeostatic model assessment (HOMA) method with the assumption that normal-weight subjects aged under 35 years have a 100% beta-cell function (HOMA-B). (NCT00700817)
Timeframe: Week 52, Week 78

Interventionpercentage point (Mean)
Sita -> Sita -> Lira 1.2 mg13.31
Sita -> Sita -> Lira 1.8 mg23.09

Mean Change in Body Weight From Week 52 to Week 78

Mean change in body weight from Week 52 to Week 78. (NCT00700817)
Timeframe: Week 52, Week 78

Interventionkg (Mean)
Sita -> Sita -> Lira 1.2 mg-1.64
Sita -> Sita -> Lira 1.8 mg-2.48

Mean Change in Diastolic Blood Pressure (DBP) From Week 52 to Week 78

Mean change in diastolic blood pressure (DBP) from Week 52 to Week 78. (NCT00700817)
Timeframe: Week 52, Week 78

InterventionmmHg (Mean)
Sita -> Sita -> Lira 1.2 mg-0.60
Sita -> Sita -> Lira 1.8 mg0.03

Mean Change in Fasting Plasma Glucose (FPG) From Week 52 to Week 78

Mean change in fasting plasma glucose (FPG) Week 52 to Week 78. (NCT00700817)
Timeframe: Week 52, Week 78

Interventionmmol/L (Mean)
Sita -> Sita -> Lira 1.2 mg-0.84
Sita -> Sita -> Lira 1.8 mg-1.42

Mean Change in Free Fatty Acids (FFA) From Week 52 to Week 78

Mean change in free fatty acids (FFA) from Week 52 to Week 78. (NCT00700817)
Timeframe: Week 52, Week 78

Interventionmmol/L (Mean)
Sita -> Sita -> Lira 1.2 mg0.02
Sita -> Sita -> Lira 1.8 mg-0.01

Mean Change in Glycosylated Haemoglobin A1c (HbA1c) From Week 52 to Week 78

Mean Change in Glycosylated Haemoglobin A1c (HbA1c) from Week 52 to Week 78 (NCT00700817)
Timeframe: Week 52, Week 78

InterventionPercentage point of total HbA1c (Mean)
Sita -> Sita -> Lira 1.2 mg-0.24
Sita -> Sita -> Lira 1.8 mg-0.45

Mean Change in High-density Lipoprotein-cholesterol (HDL-C) From Week 52 to Week 78

Mean change in high-density lipoprotein-cholesterol (HDL-C) from Week 52 to Week 78. (NCT00700817)
Timeframe: Week 52, Week 78

Interventionmmol/L (Mean)
Sita -> Sita -> Lira 1.2 mg0.02
Sita -> Sita -> Lira 1.8 mg-0.01

Mean Change in Low-density Lipoprotein-cholesterol (LDL-C) From Week 52 to Week 78

Mean change in low-density lipoprotein-cholesterol (LDL-C) from week 52 to Week 78. (NCT00700817)
Timeframe: Week 52, Week 78

Interventionmmol/L (Mean)
Sita -> Sita -> Lira 1.2 mg-0.22
Sita -> Sita -> Lira 1.8 mg-0.25

Mean Change in Overall Treatment Satisfaction (OTS) From Week 52 to Week 78

The Overall Treatment Satisfaction is a sum of 6 items from the Diabetes Treatment Satisfaction Questionnaire, which is a self-assessment of treatment satisfaction. The scale of each sub-item goes from 0 (lowest satisfaction) to 6 (highest satisfaction) and the overall scale of OTS therefore goes from 0 to 36. (NCT00700817)
Timeframe: Week 52, Week 78

Interventionscores on a scale (Mean)
Sita -> Sita -> Lira 1.2 mg1.48
Sita -> Sita -> Lira 1.8 mg0.98

Mean Change in Pulse From Week 52 to Week 78

Mean change in pulse from Week 52 to Week 78. (NCT00700817)
Timeframe: Week 52, Week 78

Interventionbeats/minute (Mean)
Sita -> Sita -> Lira 1.2 mg0.90
Sita -> Sita -> Lira 1.8 mg2.19

Mean Change in Systolic Blood Pressure (SBP) From Week 52 to Week 78

Mean change in systolic blood pressure (SBP) from Week 52 to Week 78. (NCT00700817)
Timeframe: Week 52, Week 78

InterventionmmHg (Mean)
Sita -> Sita -> Lira 1.2 mg-2.12
Sita -> Sita -> Lira 1.8 mg0.35

Mean Change in Total Cholesterol From Week 52 to Week 78

Mean change in total cholesterol from Week 52 to Week 78 (NCT00700817)
Timeframe: Week 52, Week 78

Interventionmmol/L (Mean)
Sita -> Sita -> Lira 1.2 mg-0.16
Sita -> Sita -> Lira 1.8 mg-0.24

Mean Change in Triglycerides (TG) From Week 52 to Week 78

Mean change in triglycerides (TG) from Week 52 to Week 78. (NCT00700817)
Timeframe: Week 52, Week 78

Interventionmmol/L (Mean)
Sita -> Sita -> Lira 1.2 mg-0.20
Sita -> Sita -> Lira 1.8 mg-0.26

Mean Change in Very Low-density Lipoprotein-cholesterol (VLDL-C) at Week 52 to Week 78

Mean change in very low-density lipoprotein-cholesterol (VLDL-C) from Week 52 to Week 78. (NCT00700817)
Timeframe: Week 52, Week 78

Interventionmmol/L (Mean)
Sita -> Sita -> Lira 1.2 mg0.03
Sita -> Sita -> Lira 1.8 mg0.02

Mean Change in Waist Circumference From Week 52 to Week 78

Mean change in Waist Circumference from Week 52 to Week 78. (NCT00700817)
Timeframe: Week 52, Week 78

Interventionkg (Mean)
Sita -> Sita -> Lira 1.2 mg-1.33
Sita -> Sita -> Lira 1.8 mg-2.05

Mean Change in Waist to Hip Ratio From Week 52 to Week 78

Mean change in Waist to Hip Ratio from Week 52 to Week 78. The measure is assessed as the circumference of the waist divided by the circumference of the hip. (NCT00700817)
Timeframe: Week 52, Week 78

Interventioncm/cm (Mean)
Sita -> Sita -> Lira 1.2 mg-0.01
Sita -> Sita -> Lira 1.8 mg-0.00

Percentage of Subjects Achieving Treatment Target of HbA1c < 7.0% at Week 26

Calculated as the percentage of subjects achieving treatment target of HbA1c < 7.0% at Week 26 (NCT00700817)
Timeframe: Week 0, Week 26

Interventionpercentage of subjects (Number)
Lira 1.2 mg -> Lira 1.2 mg -> Lira 1.2 mg43
Lira 1.8 mg -> Lira 1.8 mg -> Lira 1.8 mg55
Sita -> Sita22

Percentage of Subjects Achieving Treatment Target of HbA1c < 7.0% at Week 52

Calculated as an estimate of the percentage of subjects achieving treatment target of HbA1c < 7.0% at Week 52 (NCT00700817)
Timeframe: Week 0, Week 52

Interventionpercentage of subjects (Number)
Lira 1.2 mg -> Lira 1.2 mg -> Lira 1.2 mg50
Lira 1.8 mg -> Lira 1.8 mg -> Lira 1.8 mg63
Sita -> Sita27

Percentage of Subjects Achieving Treatment Target of HbA1c < 7.0% at Week 78

Calculated as an estimate of the percentage of subjects achieving treatment target of HbA1c < 7.0% at Week 78. Based on the extension 2 FAS. (NCT00700817)
Timeframe: Week 0, Week 78

Interventionpercentage of subjects (Number)
Sita -> Sita -> Lira 1.2 mg49
Sita -> Sita -> Lira 1.8 mg50

Percentage of Subjects Achieving Treatment Target of HbA1c < 7.0% at Week 78

Calculated as an estimate of the percentage of subjects achieving treatment target of HbA1c < 7.0% at Week 78. Based on the FAS. (NCT00700817)
Timeframe: Week 0, Week 78

Interventionpercentage of subjects (Number)
Lira 1.2 mg -> Lira 1.2 mg -> Lira 1.2 mg35
Lira 1.8 mg -> Lira 1.8 mg -> Lira 1.8 mg51

Percentage of Subjects Achieving Treatment Target of HbA1c =< 6.5% at Week 26

Calculated as the percentage of subjects achieving treatment target of HbA1c =< 6.5% at Week 26 (NCT00700817)
Timeframe: Week 0, Week 26

Interventionpercentage of subjects (Number)
Lira 1.2 mg -> Lira 1.2 mg -> Lira 1.2 mg23
Lira 1.8 mg -> Lira 1.8 mg -> Lira 1.8 mg36
Sita -> Sita12

Percentage of Subjects Achieving Treatment Target of HbA1c =< 6.5% at Week 52

Calculated as an estimate of the percentage of subjects achieving treatment target of HbA1c =< 6.5% at Week 52 (NCT00700817)
Timeframe: Week 0, Week 52

Interventionpercentage of subjects (Number)
Lira 1.2 mg -> Lira 1.2 mg -> Lira 1.2 mg24
Lira 1.8 mg -> Lira 1.8 mg -> Lira 1.8 mg40
Sita -> Sita17

Percentage of Subjects Achieving Treatment Target of HbA1c =< 6.5% at Week 78

Calculated as an estimate of the percentage of subjects achieving treatment target of HbA1c =< 6.5% at Week 78. Based on the extension 2 FAS. (NCT00700817)
Timeframe: Week 0, Week 78

Interventionpercentage of subjects (Number)
Sita -> Sita -> Lira 1.2 mg29
Sita -> Sita -> Lira 1.8 mg25

Percentage of Subjects Achieving Treatment Target of HbA1c =< 6.5% at Week 78

Calculated as an estimate of the percentage of subjects achieving treatment target of HbA1c =< 6.5% at Week 78. Based on the FAS. (NCT00700817)
Timeframe: Week 0, Week 78

Interventionpercentage of subjects (Number)
Lira 1.2 mg -> Lira 1.2 mg -> Lira 1.2 mg12
Lira 1.8 mg -> Lira 1.8 mg -> Lira 1.8 mg27

Hypoglycaamic Episodes, Weeks 52-78

Number of hypoglycaemic episodes from Week 52 to Week 78, defined as major, minor, or symptoms only. Major if unable to treat her/himself. Minor if able to treat her/himself and plasma glucose below 3.1 mmol/L. Symptoms only if able to treat her/himself and no plasma glucose measurement or plasma glucose higher than or equal to 3.1 mmol/L. (NCT00700817)
Timeframe: Week 52-78

,,,
Interventionepisodes (Number)
MajorMinorSymptoms onlyUnclassified
Lira 1.2 mg -> Lira 1.2 mg -> Lira 1.2 mg11230
Lira 1.8 mg -> Lira 1.8 mg -> Lira 1.8 mg05110
Sita -> Sita -> Lira 1.2 mg0310
Sita -> Sita -> Lira 1.8 mg0600

Hypoglycaemic Episodes (Excluding Outlier Subject), Weeks 0-26

Number of hypoglycaemic episodes from Week 0 to Week 26, defined as major, minor, or symptoms only. Major if unable to treat her/himself. Minor if able to treat her/himself and plasma glucose below 3.1 mmol/L. Symptoms only if able to treat her/himself and no plasma glucose measurement or plasma glucose higher than or equal to 3.1 mmol/L. (NCT00700817)
Timeframe: Weeks 0-26

,,
Interventionepisodes (Number)
MajorMinorSymptoms onlyUnclassified
Lira 1.2 mg -> Lira 1.2 mg -> Lira 1.2 mg117120
Lira 1.8 mg -> Lira 1.8 mg -> Lira 1.8 mg016151
Sita -> Sita011100

Hypoglycaemic Episodes (Excluding Outlier Subject), Weeks 0-52

Number of hypoglycaemic episodes from Week 0 to Week 52, defined as major, minor, or symptoms only. Major if unable to treat her/himself. Minor if able to treat her/himself and plasma glucose below 3.1 mmol/L. Symptoms only if able to treat her/himself and no plasma glucose measurement or plasma glucose higher than or equal to 3.1 mmol/L. (NCT00700817)
Timeframe: Weeks 0-52

,,
Interventionepisodes (Number)
MajorMinorSymptoms onlyUnclassified
Lira 1.2 mg -> Lira 1.2 mg -> Lira 1.2 mg124140
Lira 1.8 mg -> Lira 1.8 mg -> Lira 1.8 mg028291
Sita -> Sita025120

Hypoglycaemic Episodes (Excluding Outlier Subject), Weeks 0-78

Number of hypoglycaemic episodes from Week 0 to Week 78, defined as major, minor, or symptoms only. Major if unable to treat her/himself. Minor if able to treat her/himself and plasma glucose below 3.1 mmol/L. Symptoms only if able to treat her/himself and no plasma glucose measurement or plasma glucose higher than or equal to 3.1 mmol/L. (NCT00700817)
Timeframe: Weeks 0-78

,,
Interventionepisodes (Number)
MajorMinorSymptoms onlyUnclassified
Lira 1.2 mg -> Lira 1.2 mg -> Lira 1.2 mg236180
Lira 1.8 mg -> Lira 1.8 mg -> Lira 1.8 mg033401
Sita -> Sita034130

Hypoglyceamic Episodes, Weeks 0-26

Number of hypoglycaemic episodes from Week 0 to Week 26, defined as major, minor, or symptoms only. Major if unable to treat her/himself. Minor if able to treat her/himself and plasma glucose below 3.1 mmol/L. Symptoms only if able to treat her/himself and no plasma glucose measurement or plasma glucose higher than or equal to 3.1 mmol/L. (NCT00700817)
Timeframe: Weeks 0-26

,,
Interventionepisodes (Number)
MajorMinorSymptoms onlyUnclassified
Lira 1.2 mg -> Lira 1.2 mg -> Lira 1.2 mg117120
Lira 1.8 mg -> Lira 1.8 mg -> Lira 1.8 mg037151
Sita -> Sita011100

Hypoglyceamic Episodes, Weeks 0-52

Number of hypoglycaemic episodes from Week 0 to Week 52, defined as major, minor, or symptoms only. Major if unable to treat her/himself. Minor if able to treat her/himself and plasma glucose below 3.1 mmol/L. Symptoms only if able to treat her/himself and no plasma glucose measurement or plasma glucose higher than or equal to 3.1 mmol/L. (NCT00700817)
Timeframe: Weeks 0-52

,,
Interventionepisodes (Number)
MajorMinorSymptoms onlyUnclassified
Lira 1.2 mg -> Lira 1.2 mg -> Lira 1.2 mg124140
Lira 1.8 mg -> Lira 1.8 mg -> Lira 1.8 mg051291
Sita -> Sita025120

Hypoglyceamic Episodes, Weeks 0-78

Number of hypoglycaemic episodes from Week 0 to Week 78, defined as major, minor, or symptoms only. Major if unable to treat her/himself. Minor if able to treat her/himself and plasma glucose below 3.1 mmol/L. Symptoms only if able to treat her/himself and no plasma glucose measurement or plasma glucose higher than or equal to 3.1 mmol/L. (NCT00700817)
Timeframe: Weeks 0-78

,,
Interventionepisodes (Number)
MajorMinorSymptoms onlyUnclassified
Lira 1.2 mg -> Lira 1.2 mg -> Lira 1.2 mg236180
Lira 1.8 mg -> Lira 1.8 mg -> Lira 1.8 mg056401
Sita -> Sita034130

Comparison of Changes in Fasting Serum Glucose (FSG)With Pioglitazone and Metformin

Response rate was defined by ≥10% decrease of FSG or/and ≥1% decrease of HbA1c from the baseline values after 3 months treatment.48 responded to pioglitazone and 32 responded to metformin. (NCT01589445)
Timeframe: 3 months for each drug

,
Interventionmmol/l (Mean)
Baseline FSG3rd Month FSG
Metformin ( 002 Group)6.26.5
Pioglitazone (001 Group)6.95.4

Comparison of Changes in Fasting Serum Insulin (FSI)With Pioglitazone and Metformin

Response rate was defined by ≥10% decrease of FSG or/and ≥1% decrease of HbA1c from the baseline values after 3 months treatment.48 responded to pioglitazone and 32 responded to metformin. (NCT01589445)
Timeframe: 3 months for each drug

,
InterventionμU/ml (Mean)
Baseline FSI3rd month FSI
Metformin ( 002 Group)13.013.9
Pioglitazone (001 Group)16.212.3

Comparison of Changes in Glycosylated Hemoglobin (HbA1c)With Pioglitazone and Metformin

Response rate was defined by ≥10% decrease of FSG or/and ≥1% decrease of HbA1c from the baseline values after 3 months treatment.48 responded to pioglitazone and 32 responded to metformin. (NCT01589445)
Timeframe: 3 months for each drug

,
Interventionpercentage (Mean)
Baseline HbA1c3rd month HbA1c
Metformin ( 002 Group)7.87.0
Pioglitazone (001 Group)7.36.7

Comparison of Changes in HOMA Percent B and HOMA Percent S With Pioglitazone and Metformin

"Response rate was defined by ≥10% decrease of FSG or/and ≥1% decrease of HbA1c from the baseline values after 3 months treatment.48 responded to pioglitazone and 32 responded to metformin.~Analysis 1: Homeostatic Model Assessment of Beta cell function(HOMA percent B) Analysis 2: Homeostatic Model Assessment of Insulin Sensitivity (Homa percent S)" (NCT01589445)
Timeframe: 3 months for each drug

,
Interventionpercentage (Mean)
Baseline HOMA percent beta cells function3rd month HOMA percent beta cells functionBaseline HOMA percent sensitivity3rd month HOMA percent sensitivity
Metformin ( 002 Group)109.3116.076.267.2
Pioglitazone (001 Group)118.9132.351.169.3

Comparison of Changes in Insulin Levels (HOMA IR,QUICKI) With Pioglitazone and Metformin

"Response rate was defined by ≥10% decrease of FSG or/and ≥1% decrease of HbA1c from the baseline values after 3 months treatment.48 responded to pioglitazone and 32 responded to metformin.~Analysis 1: Homeostasis Model Assessment Insulin Resistance(HOMA IR) Analysis 2: Quantitative Insulin sensitivity Check Index(QUICKI)" (NCT01589445)
Timeframe: 3 months for each drug

,
InterventionScore on a scale ( SI unit) (Mean)
Baseline QUICKI3rd month QUICKIBaseline HOMA IR3rd month HOMA IR
Metformin ( 002 Group)0.570.543.74.3
Pioglitazone (001 Group)0.520.595.12.9

Comparison of Changes in Lipid Profiles With Pioglitazone and Metformin

"Response rate was defined by ≥10% decrease of FSG or/and ≥1% decrease of HbA1c from the baseline values after 3 months treatment.48 responded to pioglitazone and 32 responded to metformin.~Analysis 1:Total Cholesterol(TC) Analysis 2:Triglyceride(TG) Analysis 3:High Density Lipoprotein(HDL) Analysis 4:Low Density Lipoprotein(LDL)" (NCT01589445)
Timeframe: 3 months for each drug

,
Interventionmg/dl (Mean)
Baseline TC3rd month TCBaseline TG3rd month TGBaseline HDL3rd month HDLBaseline LDL3rd month LDL
Metformin (002 Group)193.0177.0166.0175.034.434.7125.6112.0
Pioglitazone (001 Group)182.01781831953333.2112.8105.5

Change in Abdominal Fat (DEXA).

A comparison between the ramelteon group and the placebo group of change in abdominal fat measured by a DEXA scan, assessed at Baseline and Week 8. (NCT00595504)
Timeframe: Baseline and Week 8

Interventiong (Mean)
Ramelteon3934.86
Placebo (Sugar Pill)5120.92

Change in Insulin Resistance as Measured by the Homeostatic Model Assessment of Insulin Resistance (HOMA-IR).

A comparison between the ramelteon group and the placebo group of change in insulin resistance measured by the homeostatic model assessment of insulin resistance (HOMA-IR), assessed at Baseline and Week 8. (NCT00595504)
Timeframe: Baseline and Week 8

InterventionHOMA score (Mean)
Ramelteon2.4
Placebo (Sugar Pill)2.36

Change in Waist Circumference

A comparison between the ramelteon group and the placebo group in change in waist circumference (measured in cm) measured at Baseline and Week 8. (NCT00595504)
Timeframe: Baseline and Week 8

Interventioncm (Mean)
Ramelteon106.09
Placebo (Sugar Pill)108.37

Change in C-Reactive Protein (CRP) From Baseline to Week 12

(NCT01082588)
Timeframe: Baseline, week 12

Interventionmg/L (Mean)
Pravastatin0.8063
Placebo-0.5136

Change in LDL-cholesterol Between Baseline and Week 12

(NCT01082588)
Timeframe: Baseline, week 12

Interventionmg/dl (Mean)
Pravastatin-25.565
Placebo-2.913

Change in MATRICS Neuropsychological Battery Composite Score From Baseline to Week 12

"The Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) Consensus Cognitive Battery measures cognitive functioning within 7 domains: speed of processing, attention/vigilance, working memory (non verbal and verbal), verbal learning, visual learning, reasoning and problem solving and social cognition.~The composite score is calculated by the MATRICS computer program, which equally weights each of the 7 domain scores. The range of composite scores is 20-80. Higher scores indicate higher levels or cognitive functioning, while lower scores indicate lower levels of cognitive functioning." (NCT01082588)
Timeframe: Baseline, week 12

InterventionScores on a scale (Mean)
Pravastatin4.0417
Placebo4.125

Change in Positive and Negative Syndrome Scale (PANSS) General Score From Baseline to Week 12

This is a subscale of the Positive and Negative Syndrome Scale (PANSS). The range for this subscale is 15-105. All items are summed to calculate the total score. Better outcomes have lower numbers and worse outcomes have higher numbers. (NCT01082588)
Timeframe: Baseline, week 12

InterventionScores on a scale (Mean)
Pravastatin-5.625
Placebo-3.76

Change in Positive and Negative Syndrome Scale (PANSS) Negative Score From Baseline to Week 12

This is a subscale of the Positive and Negative Syndrome Scale (PANSS). The range for this subscale is 7-49. All items are summed to calculate the total score. Better outcomes have lower numbers and worse outcomes have higher numbers. (NCT01082588)
Timeframe: Baseline, week 12

InterventionScores on a scale (Mean)
Pravastatin-0.83
Placebo-0.28

Change in Positive and Negative Syndrome Scale (PANSS) Positive Score From Baseline to Week 12

This is a subscale of the Positive and Negative Syndrome Scale (PANSS). The range for this subscale is 7-49. All items are summed to calculate the total score. Better outcomes have lower numbers and worse outcomes have higher numbers. (NCT01082588)
Timeframe: Baseline, week 12

InterventionScores on a scale (Mean)
Pravastatin-2.9583
Placebo-2.44

Change in Positive and Negative Syndrome Scale (PANSS) Total Score From Baseline to Week 12

The Positive and Negative Syndrome Scale (PANSS) is a scale used to rate severity of schizophrenia. All items are summed to calculate the total score. The scale range is 30-210. Better outcomes have lower numbers and worse outcomes have higher numbers. (NCT01082588)
Timeframe: Baseline, week 12

InterventionScores on a scale (Mean)
Pravastatin-9.416
Placebo-6.48

Change From Baseline in 2 Hr-PMG at Week 18

Change from baseline at Week 18 is defined as Week 18 minus Week 0. (NCT00337610)
Timeframe: Baseline and Week 18

Interventionmg/dL (Least Squares Mean)
Sitagliptin 100 mg-67.6
Placebo-13.5

Change From Baseline in A1C at Week 18

A1C was measured as a percent. Thus, this change from baseline reflects the Week 18 A1C percent minus the Week 0 A1C percent. (NCT00337610)
Timeframe: Baseline and Week 18

InterventionPercent (Least Squares Mean)
Sitagliptin 100 mg-1.00
Placebo0.02

Change From Baseline in A1C at Week 30

A1C was measured as a percent. Thus, this change from baseline reflects the Week 30 A1C percent minus the Week 0 A1C percent. (NCT00337610)
Timeframe: Baseline and Week 30

InterventionPercent (Least Squares Mean)
Sitagliptin 100 mg-0.98
Placebo0.04

Change From Baseline in FPG at Week 18

Change from baseline at Week 18 is defined as Week 18 FPG minus Week 0 FPG. (NCT00337610)
Timeframe: Baseline and Week 18

Interventionmg/dL (Least Squares Mean)
Sitagliptin 100 mg-32.0
Placebo-6.5

2-hour Post-meal Glucose (PMG) at Week 18

The change from baseline is the Week 18 PMG minus the Week 0 PMG. (NCT00541775)
Timeframe: Baseline and 18 Weeks

Interventionmg/dL (Least Squares Mean)
Sitagliptin-35.4
Rosiglitazone-51.3
Placebo-4.9

Fasting Plasma Glucose (FPG) at Week 18

The change from baseline is the Week 18 FPG minus the Week 0 FPG. (NCT00541775)
Timeframe: Baseline and 18 Weeks

Interventionmg/dL (Least Squares Mean)
Sitagliptin-11.7
Rosiglitazone-24.5
Placebo6.1

Hemoglobin A1C (A1C) at Week 18

"A1C is measured as percent. Thus, this change from baseline reflects the Week 18 A1C percent minus the Week 0 A1C percent.~The study hypothesis comparison was between sitagliptin versus placebo." (NCT00541775)
Timeframe: Baseline and 18 Weeks

InterventionPercent of glycosylated hemoglobin (A1C) (Least Squares Mean)
Sitagliptin-0.73
Rosiglitazone-0.79
Placebo-0.22

Concentration of Metformin in Adipose Tissue

To determine the concentration of metformin in adipose tissue. (NCT03477162)
Timeframe: Within 7 days from surgery

Interventionng/g (Median)
Metformin70

Concentration of Metformin in Plasma.

To determine the concentration of metformin in plasma. (NCT03477162)
Timeframe: Within 7 days from surgery

Interventionng/mL (Median)
Metformin450

Concentration of Metformin in Tumor-adjacent Normal Tissue

To determine the concentration of metformin in tumor-adjacent normal tissue. (NCT03477162)
Timeframe: Within 7 days from surgery

Interventionng/g (Median)
Metformin749

Concentration of Metformin in Whole Blood.

To determine the concentration of metformin in whole blood. (NCT03477162)
Timeframe: Within 7 days from surgery

Interventionng/mL (Median)
Metformin514

Lung Tumor Tissue Concentration of Metformin

To determine the intra-tumor concentrations of metformin, with a standard deviation ≤25% of the mean, in patients with solid tumors of thoracic origin administered metformin extended release. (NCT03477162)
Timeframe: Within 7 days from surgery

Interventionng/g (Median)
Metformin1290

Reviews

92 reviews available for metformin and Body Weight

ArticleYear
Impact of pharmacological interventions on anthropometric indices in women with polycystic ovary syndrome: A systematic review and meta-analysis of randomized controlled trials.
    Clinical endocrinology, 2022, Volume: 96, Issue:6

    Topics: Acarbose; Body Weight; Female; Humans; Hypoglycemic Agents; Metformin; Orlistat; Pioglitazone; Polyc

2022
Efficacy and safety of combination therapy with vildagliptin and metformin vs. metformin monotherapy for Type 2 Diabetes Mellitus therapy: a meta-analysis.
    European review for medical and pharmacological sciences, 2022, Volume: 26, Issue:8

    Topics: Blood Glucose; Body Weight; Diabetes Mellitus, Type 2; Diarrhea; Dizziness; Drug Therapy, Combinatio

2022
Efficacy and Safety of Triple Therapy with SGLT-2 Inhibitor, DPP-4 Inhibitor, and Metformin in Type 2 Diabetes: A Meta-Analysis.
    Alternative therapies in health and medicine, 2023, Volume: 29, Issue:5

    Topics: Blood Glucose; Body Weight; Diabetes Mellitus, Type 2; Dipeptidyl-Peptidase IV Inhibitors; Drug Ther

2023
Comparative efficacy and safety profile of once-weekly Semaglutide versus once-daily Sitagliptin as an add-on to metformin in patients with type 2 diabetes: a systematic review and meta-analysis.
    Annals of medicine, 2023, Volume: 55, Issue:2

    Topics: Body Weight; Diabetes Mellitus, Type 2; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Metformin;

2023
Comparison of the efficacy and safety of 10 glucagon-like peptide-1 receptor agonists as add-on to metformin in patients with type 2 diabetes: a systematic review.
    Frontiers in endocrinology, 2023, Volume: 14

    Topics: Body Weight; Diabetes Mellitus, Type 2; Exenatide; Glucagon-Like Peptide-1 Receptor; Glycated Hemogl

2023
Efficacy and safety of ipragliflozin as add-on to metformin for type 2 diabetes: a meta-analysis of double-blind randomized controlled trials.
    Postgraduate medicine, 2019, Volume: 131, Issue:8

    Topics: Blood Glucose; Blood Pressure; Body Weight; Diabetes Mellitus, Type 2; Double-Blind Method; Drug The

2019
Diabetes drugs for nonalcoholic fatty liver disease: a systematic review.
    Systematic reviews, 2019, 11-29, Volume: 8, Issue:1

    Topics: Blood Glucose; Body Weight; Exenatide; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Liraglutide

2019
Liraglutide: New Perspectives for the Treatment of Polycystic Ovary Syndrome.
    Clinical drug investigation, 2020, Volume: 40, Issue:8

    Topics: Adult; Body Mass Index; Body Weight; Diabetes Mellitus, Type 2; Double-Blind Method; Female; Humans;

2020
Efficacy and safety of dapagliflozin plus saxagliptin vs monotherapy as added to metformin in patients with type 2 diabetes: A meta-analysis.
    Medicine, 2020, Jul-24, Volume: 99, Issue:30

    Topics: Adamantane; Benzhydryl Compounds; Blood Glucose; Blood Pressure; Body Weight; Diabetes Mellitus, Typ

2020
Time course and dose effect of metformin on weight in patients with different disease states.
    Expert review of clinical pharmacology, 2020, Volume: 13, Issue:10

    Topics: Antipsychotic Agents; Body Weight; Diabetes Mellitus, Type 2; Dose-Response Relationship, Drug; Huma

2020
Durability of glycaemic control in type 2 diabetes: A systematic review and meta-analysis for its association with body weight changes.
    Diabetes, obesity & metabolism, 2021, Volume: 23, Issue:1

    Topics: Blood Glucose; Body Weight; Diabetes Mellitus, Type 2; Dipeptidyl-Peptidase IV Inhibitors; Drug Ther

2021
Effects of metformin on body weight in polycystic ovary syndrome patients: model-based meta-analysis.
    Expert review of clinical pharmacology, 2021, Volume: 14, Issue:1

    Topics: Body Mass Index; Body Weight; Dose-Response Relationship, Drug; Female; Humans; Hypoglycemic Agents;

2021
Is metformin effective for reducing weight in obese or overweight adolescents?
    The Journal of family practice, 2021, Volume: 70, Issue:2

    Topics: Adolescent; Body Mass Index; Body Weight; Humans; Hypoglycemic Agents; Metformin; Pediatric Obesity;

2021
Efficacy of Various Hypoglycemic Agents in the Treatment of Patients With Nonalcoholic Liver Disease With or Without Diabetes: A Network Meta-Analysis.
    Frontiers in endocrinology, 2021, Volume: 12

    Topics: Alanine Transaminase; Aspartate Aminotransferases; Bayes Theorem; Blood Glucose; Body Mass Index; Bo

2021
Clinical Perspectives on the Use of Subcutaneous and Oral Formulations of Semaglutide.
    Frontiers in endocrinology, 2021, Volume: 12

    Topics: Administration, Oral; Body Weight; Cardiovascular Diseases; Comorbidity; Decision Making; Diabetes M

2021
Screening for Obesity and Intervention for Weight Management in Children and Adolescents: Evidence Report and Systematic Review for the US Preventive Services Task Force.
    JAMA, 2017, Jun-20, Volume: 317, Issue:23

    Topics: Adolescent; Advisory Committees; Anti-Obesity Agents; Body Mass Index; Body Weight; Child; Child, Pr

2017
Screening for Obesity and Intervention for Weight Management in Children and Adolescents: Evidence Report and Systematic Review for the US Preventive Services Task Force.
    JAMA, 2017, Jun-20, Volume: 317, Issue:23

    Topics: Adolescent; Advisory Committees; Anti-Obesity Agents; Body Mass Index; Body Weight; Child; Child, Pr

2017
Screening for Obesity and Intervention for Weight Management in Children and Adolescents: Evidence Report and Systematic Review for the US Preventive Services Task Force.
    JAMA, 2017, Jun-20, Volume: 317, Issue:23

    Topics: Adolescent; Advisory Committees; Anti-Obesity Agents; Body Mass Index; Body Weight; Child; Child, Pr

2017
Screening for Obesity and Intervention for Weight Management in Children and Adolescents: Evidence Report and Systematic Review for the US Preventive Services Task Force.
    JAMA, 2017, Jun-20, Volume: 317, Issue:23

    Topics: Adolescent; Advisory Committees; Anti-Obesity Agents; Body Mass Index; Body Weight; Child; Child, Pr

2017
Clinical implications of current cardiovascular outcome trials with sodium glucose cotransporter-2 (SGLT2) inhibitors.
    Atherosclerosis, 2018, Volume: 272

    Topics: Albuminuria; Atherosclerosis; Benzhydryl Compounds; Body Weight; Canagliflozin; Cardiovascular Disea

2018
Understanding the impact of commonly utilized, non-insulin, glucose-lowering drugs on body weight in patients with type 2 diabetes.
    Expert opinion on pharmacotherapy, 2018, Volume: 19, Issue:10

    Topics: Benzhydryl Compounds; Body Weight; Diabetes Mellitus, Type 2; Dipeptidyl-Peptidase IV Inhibitors; Ex

2018
The safety of empagliflozin plus metformin for the treatment of type 2 diabetes.
    Expert opinion on drug safety, 2018, Volume: 17, Issue:8

    Topics: Aged; Benzhydryl Compounds; Blood Glucose; Blood Pressure; Body Weight; Diabetes Mellitus, Type 2; D

2018
Comparison of antidiabetic drugs added to sulfonylurea monotherapy in patients with type 2 diabetes mellitus: A network meta-analysis.
    PloS one, 2018, Volume: 13, Issue:8

    Topics: Blood Glucose; Body Weight; Diabetes Mellitus, Type 2; Dipeptidyl-Peptidase IV Inhibitors; Drug Comb

2018
    MMW Fortschritte der Medizin, 2018, Volume: 160, Issue:19

    Topics: Body Weight; Child; Humans; Metformin; Obesity

2018
Body Weight Considerations in the Management of Type 2 Diabetes.
    Advances in therapy, 2019, Volume: 36, Issue:1

    Topics: Blood Glucose; Body Weight; Diabetes Complications; Diabetes Mellitus, Type 2; Dipeptidyl-Peptidase

2019
Metformin induces significant reduction of body weight, total cholesterol and LDL levels in the elderly - A meta-analysis.
    PloS one, 2018, Volume: 13, Issue:11

    Topics: Aged; Aged, 80 and over; Anti-Obesity Agents; Anticholesteremic Agents; Body Weight; Cholesterol; Hu

2018
Efficacy of Metformin Treatment with Respect to Weight Reduction in Children and Adults with Obesity: A Systematic Review.
    Drugs, 2018, Volume: 78, Issue:18

    Topics: Adult; Body Mass Index; Body Weight; Child; Diabetes Mellitus, Type 2; Dose-Response Relationship, D

2018
Cost-effectiveness analysis of dapagliflozin treatment versus metformin treatment in Chinese population with type 2 diabetes.
    Journal of medical economics, 2019, Volume: 22, Issue:4

    Topics: Administration, Oral; Age Factors; Age of Onset; Benzhydryl Compounds; Body Weight; China; Cholester

2019
Sodium-Glucose Co-Transporter 2 Inhibitors Compared with Sulfonylureas in Patients with Type 2 Diabetes Inadequately Controlled on Metformin: A Meta-Analysis of Randomized Controlled Trials.
    Clinical drug investigation, 2019, Volume: 39, Issue:6

    Topics: Blood Glucose; Blood Pressure; Body Weight; Diabetes Mellitus, Type 2; Humans; Hypoglycemia; Hypogly

2019
[Management of type 2 diabetes: new or previous agents, how to choose?].
    Presse medicale (Paris, France : 1983), 2013, Volume: 42, Issue:5

    Topics: Administration, Oral; Body Weight; Diabetes Complications; Diabetes Mellitus, Type 2; Dipeptidyl-Pep

2013
Efficacy and safety of dipeptidyl peptidase-4 inhibitors and metformin as initial combination therapy and as monotherapy in patients with type 2 diabetes mellitus: a meta-analysis.
    Diabetes, obesity & metabolism, 2014, Volume: 16, Issue:1

    Topics: Blood Glucose; Body Weight; Diabetes Mellitus, Type 2; Dipeptidyl-Peptidase IV Inhibitors; Drug Ther

2014
Comparative effects of sitagliptin and metformin in patients with type 2 diabetes mellitus: a meta-analysis.
    Current medical research and opinion, 2013, Volume: 29, Issue:11

    Topics: Body Mass Index; Body Weight; Diabetes Mellitus, Type 2; Glycated Hemoglobin; Humans; Hypoglycemic A

2013
What are the preferred strategies for control of glycaemic variability in patients with type 2 diabetes mellitus?
    Diabetes, obesity & metabolism, 2013, Volume: 15 Suppl 2

    Topics: Blood Glucose; Body Weight; Diabetes Mellitus, Type 2; Diet, Reducing; Dipeptidyl-Peptidase IV Inhib

2013
[SGLT-2 inhibitors: diabetes treatment by glycosuria; literature review on the effect of dapagliflozin].
    Nederlands tijdschrift voor geneeskunde, 2013, Volume: 157, Issue:38

    Topics: Benzhydryl Compounds; Blood Glucose; Body Weight; Diabetes Mellitus, Type 2; Glucosides; Glycated He

2013
Dapagliflozin compared with other oral anti-diabetes treatments when added to metformin monotherapy: a systematic review and network meta-analysis.
    Diabetes, obesity & metabolism, 2014, Volume: 16, Issue:5

    Topics: Administration, Oral; Benzhydryl Compounds; Blood Glucose; Body Weight; Diabetes Mellitus, Type 2; D

2014
[Oral add-on therapy to metformin in type 2 diabetes mellitus: a direct comparison between canagliflozin and sitagliptin].
    Deutsche medizinische Wochenschrift (1946), 2014, Volume: 139 Suppl 2

    Topics: Administration, Oral; Adolescent; Adult; Aged; Aged, 80 and over; Blood Glucose; Blood Pressure; Bod

2014
Combinational therapy with metformin and sodium-glucose cotransporter inhibitors in management of type 2 diabetes: systematic review and meta-analyses.
    Diabetes research and clinical practice, 2014, Volume: 105, Issue:3

    Topics: Adult; Aged; Benzhydryl Compounds; Blood Glucose; Blood Pressure; Body Weight; Canagliflozin; Diabet

2014
Efficacy and safety of basal insulin glargine 12 and 24 weeks after initiation in persons with type 2 diabetes: a pooled analysis of data from treatment arms of 15 treat-to-target randomised controlled trials.
    Diabetes research and clinical practice, 2014, Volume: 106, Issue:2

    Topics: Blood Glucose; Body Weight; Diabetes Mellitus, Type 2; Female; Follow-Up Studies; Glycated Hemoglobi

2014
Comparative efficacy and safety of antidiabetic drug regimens added to metformin monotherapy in patients with type 2 diabetes: a network meta-analysis.
    PloS one, 2015, Volume: 10, Issue:4

    Topics: Blood Pressure; Body Weight; Diabetes Mellitus, Type 2; Drug Therapy, Combination; Glycated Hemoglob

2015
[Metformin: new data for an old molecule].
    Revue medicale suisse, 2015, Jun-03, Volume: 11, Issue:477

    Topics: Blood Glucose; Body Weight; Cardiovascular Diseases; Diabetes Mellitus, Type 2; Humans; Hypoglycemic

2015
Evaluating the Effects of Metformin Use on Height in Children and Adolescents: A Meta-analysis of Randomized Clinical Trials.
    JAMA pediatrics, 2015, Volume: 169, Issue:11

    Topics: Adolescent; Body Height; Body Mass Index; Body Weight; Child; Female; Humans; Hypoglycemic Agents; M

2015
GLP-1 Receptor Agonists: Practical Considerations for Clinical Practice.
    The Diabetes educator, 2015, Volume: 41, Issue:1 Suppl

    Topics: Blood Glucose; Blood Pressure; Body Weight; Cardiovascular Diseases; Diabetes Mellitus, Type 2; Drug

2015
Dipeptidyl Peptidase-4 Inhibitors in Diverse Patient Populations With Type 2 Diabetes.
    The Diabetes educator, 2015, Volume: 41, Issue:1 Suppl

    Topics: Age Factors; Aged; Aged, 80 and over; Blood Glucose; Body Weight; Diabetes Mellitus, Type 2; Dipepti

2015
Efficacy and safety of dulaglutide in patients with type 2 diabetes: a meta-analysis and systematic review.
    Scientific reports, 2016, Jan-08, Volume: 6

    Topics: Blood Glucose; Body Weight; Diabetes Mellitus, Type 2; Exenatide; Glucagon-Like Peptides; Glycated H

2016
Mono-ovulation in women with polycystic ovary syndrome: a clinical review on ovulation induction.
    Reproductive biomedicine online, 2016, Volume: 32, Issue:6

    Topics: Adult; Anovulation; Body Weight; Clomiphene; Female; Fertility Agents, Female; Gonadotropins; Humans

2016
Pharmacologic Therapy of Type 2 Diabetes.
    The Medical clinics of North America, 2016, Volume: 100, Issue:4

    Topics: Aging; Blood Glucose; Body Weight; Diabetes Mellitus, Type 2; Dipeptidyl-Peptidase IV Inhibitors; Dr

2016
Metformin for Clozapine Associated Obesity: A Systematic Review and Meta-Analysis.
    PloS one, 2016, Volume: 11, Issue:6

    Topics: Antipsychotic Agents; Blood Glucose; Body Mass Index; Body Weight; Clozapine; Fasting; Humans; Hypog

2016
Beneficial effect of lixisenatide after 76 weeks of treatment in patients with type 2 diabetes mellitus: A meta-analysis from the GetGoal programme.
    Diabetes, obesity & metabolism, 2017, Volume: 19, Issue:2

    Topics: Adult; Aged; Blood Glucose; Body Weight; Diabetes Mellitus, Type 2; Drug Therapy, Combination; Femal

2017
Empagliflozin/metformin fixed-dose combination: a review in patients with type 2 diabetes.
    Expert opinion on pharmacotherapy, 2016, Volume: 17, Issue:18

    Topics: Benzhydryl Compounds; Blood Glucose; Blood Pressure; Body Weight; Diabetes Mellitus, Type 2; Drug Co

2016
Fixed-Dose Combination of Canagliflozin and Metformin for the Treatment of Type 2 Diabetes: An Overview.
    Advances in therapy, 2017, Volume: 34, Issue:1

    Topics: Blood Glucose; Blood Pressure; Body Weight; Canagliflozin; Clinical Trials, Phase III as Topic; Diab

2017
Combination treatment in the management of type 2 diabetes: focus on vildagliptin and metformin as a single tablet.
    Vascular health and risk management, 2008, Volume: 4, Issue:3

    Topics: Adamantane; Body Weight; Diabetes Mellitus, Type 2; Dipeptidyl-Peptidase IV Inhibitors; Disease Prog

2008
Drug evaluation: vildagliptin-metformin single-tablet combination.
    Advances in therapy, 2009, Volume: 26, Issue:2

    Topics: Adamantane; Body Weight; Diabetes Mellitus, Type 2; Dipeptidyl-Peptidase IV Inhibitors; Drug Combina

2009
Metformin--the gold standard in type 2 diabetes: what does the evidence tell us?
    Diabetes, obesity & metabolism, 2009, Volume: 11 Suppl 2

    Topics: Body Weight; Diabetes Mellitus, Type 2; Evidence-Based Medicine; Humans; Hypoglycemic Agents; Metfor

2009
Diabetes medications and body weight.
    Expert opinion on drug safety, 2009, Volume: 8, Issue:5

    Topics: Abdominal Fat; Benzamides; Body Weight; Clinical Trials as Topic; Diabetes Mellitus, Type 2; Dipepti

2009
Effects of pioglitazone and rosiglitazone combined with metformin on body weight in people with diabetes.
    Diabetes, obesity & metabolism, 2009, Volume: 11, Issue:12

    Topics: Blood Glucose; Body Weight; Diabetes Mellitus, Type 2; Drug Therapy, Combination; Female; Humans; Hy

2009
Changes in weight and metabolic parameters during treatment with antipsychotics and metformin: do the data inform as to potential guideline development? A systematic review of clinical studies.
    International journal of clinical practice, 2009, Volume: 63, Issue:12

    Topics: Antipsychotic Agents; Appetite Depressants; Blood Glucose; Body Weight; Double-Blind Method; Humans;

2009
The effect of metformin on anthropometrics and insulin resistance in patients receiving atypical antipsychotic agents: a meta-analysis.
    The Journal of clinical psychiatry, 2010, Volume: 71, Issue:10

    Topics: Anthropometry; Antipsychotic Agents; Body Mass Index; Body Weight; Diabetes Mellitus, Type 2; Humans

2010
Thiazolidinediones plus metformin association on body weight in patients with type 2 diabetes.
    Diabetes research and clinical practice, 2011, Volume: 91, Issue:3

    Topics: Body Weight; Diabetes Mellitus, Type 2; Drug Therapy, Combination; Humans; Hypoglycemic Agents; Metf

2011
The adjunctive use of metformin to treat or prevent atypical antipsychotic-induced weight gain: a review.
    Journal of psychiatric practice, 2010, Volume: 16, Issue:5

    Topics: Antipsychotic Agents; Blood Glucose; Body Weight; Humans; Hypoglycemic Agents; Metformin; Obesity; O

2010
Early clinical studies with liraglutide.
    International journal of clinical practice. Supplement, 2010, Issue:167

    Topics: Blood Glucose; Body Weight; Cardiotonic Agents; Cardiovascular Diseases; Clinical Trials, Phase I as

2010
Optimizing outcomes for GLP-1 agonists.
    The Journal of the American Osteopathic Association, 2011, Volume: 111, Issue:2 Suppl 1

    Topics: Algorithms; Blood Glucose; Body Weight; Diabetes Mellitus, Type 2; Exenatide; Glucagon-Like Peptide

2011
Weight beneficial treatments for type 2 diabetes.
    The Journal of clinical endocrinology and metabolism, 2011, Volume: 96, Issue:11

    Topics: Body Weight; Diabetes Mellitus, Type 2; Glucagon-Like Peptide 1; Humans; Hypoglycemic Agents; Insuli

2011
Second-line therapy in patients with type 2 diabetes inadequately controlled with metformin monotherapy: a systematic review and mixed-treatment comparison meta-analysis.
    Open medicine : a peer-reviewed, independent, open-access journal, 2011, Volume: 5, Issue:1

    Topics: Bayes Theorem; Body Weight; Confidence Intervals; Diabetes Mellitus, Type 2; Dipeptidyl-Peptidase IV

2011
Dipeptidyl peptidase-4 inhibitors for treatment of type 2 diabetes mellitus in the clinical setting: systematic review and meta-analysis.
    BMJ (Clinical research ed.), 2012, Mar-12, Volume: 344

    Topics: Adult; Blood Glucose; Body Weight; Diabetes Mellitus, Type 2; Dipeptidyl-Peptidase IV Inhibitors; Di

2012
Dipeptidyl peptidase-4 inhibitors for treatment of type 2 diabetes mellitus in the clinical setting: systematic review and meta-analysis.
    BMJ (Clinical research ed.), 2012, Mar-12, Volume: 344

    Topics: Adult; Blood Glucose; Body Weight; Diabetes Mellitus, Type 2; Dipeptidyl-Peptidase IV Inhibitors; Di

2012
Dipeptidyl peptidase-4 inhibitors for treatment of type 2 diabetes mellitus in the clinical setting: systematic review and meta-analysis.
    BMJ (Clinical research ed.), 2012, Mar-12, Volume: 344

    Topics: Adult; Blood Glucose; Body Weight; Diabetes Mellitus, Type 2; Dipeptidyl-Peptidase IV Inhibitors; Di

2012
Dipeptidyl peptidase-4 inhibitors for treatment of type 2 diabetes mellitus in the clinical setting: systematic review and meta-analysis.
    BMJ (Clinical research ed.), 2012, Mar-12, Volume: 344

    Topics: Adult; Blood Glucose; Body Weight; Diabetes Mellitus, Type 2; Dipeptidyl-Peptidase IV Inhibitors; Di

2012
Dipeptidyl peptidase-4 inhibitors for treatment of type 2 diabetes mellitus in the clinical setting: systematic review and meta-analysis.
    BMJ (Clinical research ed.), 2012, Mar-12, Volume: 344

    Topics: Adult; Blood Glucose; Body Weight; Diabetes Mellitus, Type 2; Dipeptidyl-Peptidase IV Inhibitors; Di

2012
Dipeptidyl peptidase-4 inhibitors for treatment of type 2 diabetes mellitus in the clinical setting: systematic review and meta-analysis.
    BMJ (Clinical research ed.), 2012, Mar-12, Volume: 344

    Topics: Adult; Blood Glucose; Body Weight; Diabetes Mellitus, Type 2; Dipeptidyl-Peptidase IV Inhibitors; Di

2012
Dipeptidyl peptidase-4 inhibitors for treatment of type 2 diabetes mellitus in the clinical setting: systematic review and meta-analysis.
    BMJ (Clinical research ed.), 2012, Mar-12, Volume: 344

    Topics: Adult; Blood Glucose; Body Weight; Diabetes Mellitus, Type 2; Dipeptidyl-Peptidase IV Inhibitors; Di

2012
Dipeptidyl peptidase-4 inhibitors for treatment of type 2 diabetes mellitus in the clinical setting: systematic review and meta-analysis.
    BMJ (Clinical research ed.), 2012, Mar-12, Volume: 344

    Topics: Adult; Blood Glucose; Body Weight; Diabetes Mellitus, Type 2; Dipeptidyl-Peptidase IV Inhibitors; Di

2012
Dipeptidyl peptidase-4 inhibitors for treatment of type 2 diabetes mellitus in the clinical setting: systematic review and meta-analysis.
    BMJ (Clinical research ed.), 2012, Mar-12, Volume: 344

    Topics: Adult; Blood Glucose; Body Weight; Diabetes Mellitus, Type 2; Dipeptidyl-Peptidase IV Inhibitors; Di

2012
Effect of antidiabetic agents added to metformin on glycaemic control, hypoglycaemia and weight change in patients with type 2 diabetes: a network meta-analysis.
    Diabetes, obesity & metabolism, 2012, Volume: 14, Issue:9

    Topics: Blood Glucose; Body Weight; Diabetes Mellitus, Type 2; Drug Therapy, Combination; Glycated Hemoglobi

2012
Metformin in obesity, cancer and aging: addressing controversies.
    Aging, 2012, Volume: 4, Issue:5

    Topics: Aging; Animals; Body Weight; Diabetes Mellitus, Type 2; Female; Humans; Hypoglycemic Agents; Metform

2012
Potential role of non-insulin adjunct therapy in Type 1 diabetes.
    Diabetic medicine : a journal of the British Diabetic Association, 2013, Volume: 30, Issue:2

    Topics: Blood Glucose; Body Weight; C-Peptide; Diabetes Mellitus, Type 1; Dipeptidyl-Peptidase IV Inhibitors

2013
Incretin-based therapy in combination with basal insulin: a promising tactic for the treatment of type 2 diabetes.
    Diabetes & metabolism, 2013, Volume: 39, Issue:1

    Topics: Blood Glucose; Body Weight; Diabetes Mellitus, Type 2; Dipeptidyl-Peptidase IV Inhibitors; Drug Ther

2013
Combination of drugs in the management of diabetes mellitus.
    Journal of the Indian Medical Association, 2002, Volume: 100, Issue:7

    Topics: Body Weight; Diabetes Mellitus; Diabetes Mellitus, Type 2; Drug Therapy, Combination; Humans; Hypogl

2002
Reducing coronary heart disease associated with type 2 diabetes: lifestyle intervention and treatment of dyslipidaemia.
    Diabetes research and clinical practice, 2003, Volume: 61 Suppl 1

    Topics: Body Weight; Clinical Trials as Topic; Coronary Disease; Diabetes Mellitus, Type 2; Drug Therapy, Co

2003
Metformin in polycystic ovary syndrome: systematic review and meta-analysis.
    BMJ (Clinical research ed.), 2003, Oct-25, Volume: 327, Issue:7421

    Topics: Blood Pressure; Body Weight; Double-Blind Method; Female; Fertility Agents, Female; Humans; Insulin;

2003
Treatment of insulin resistance in diabetes mellitus.
    European journal of pharmacology, 2004, Apr-19, Volume: 490, Issue:1-3

    Topics: Anti-Inflammatory Agents; Body Weight; Diabetes Mellitus, Type 2; Female; Humans; Hyperglycemia; Hyp

2004
Metformin in polycystic ovary syndrome.
    Current opinion in obstetrics & gynecology, 2004, Volume: 16, Issue:6

    Topics: Anovulation; Body Weight; Clomiphene; Drug Therapy, Combination; Female; Fertility Agents, Female; G

2004
Tolerability profile of metformin/glibenclamide combination tablets (Glucovance): a new treatment for the management of type 2 diabetes mellitus.
    Drug safety, 2004, Volume: 27, Issue:15

    Topics: Body Weight; Diabetes Mellitus, Type 2; Dose-Response Relationship, Drug; Double-Blind Method; Drug

2004
Treating insulin resistance in type 2 diabetes with metformin and thiazolidinediones.
    Diabetes, obesity & metabolism, 2005, Volume: 7, Issue:6

    Topics: Body Weight; Diabetes Mellitus, Type 2; Drug Monitoring; Drug Therapy, Combination; Humans; Hypergly

2005
Insulin-sensitisers in the treatment of polycystic ovary syndrome.
    Expert opinion on pharmacotherapy, 2005, Volume: 6, Issue:14

    Topics: Body Weight; Cardiovascular Diseases; Diabetes Mellitus, Type 2; Diet; Drug Approval; Exercise; Fema

2005
Pioglitazone: an antidiabetic drug with cardiovascular therapeutic effects.
    Expert review of cardiovascular therapy, 2006, Volume: 4, Issue:4

    Topics: Body Weight; Cardiovascular Diseases; Cardiovascular System; Diabetes Mellitus; Diabetic Angiopathie

2006
Lifestyle choices, diet, and insulin sensitizers in polycystic ovary syndrome.
    Endocrine, 2006, Volume: 30, Issue:1

    Topics: Age Factors; Alcohol Drinking; Body Weight; Caffeine; Female; Humans; Hypoglycemic Agents; Infertili

2006
Lifestyle choices, diet, and insulin sensitizers in polycystic ovary syndrome.
    Endocrine, 2006, Volume: 30, Issue:1

    Topics: Age Factors; Alcohol Drinking; Body Weight; Caffeine; Female; Humans; Hypoglycemic Agents; Infertili

2006
Lifestyle choices, diet, and insulin sensitizers in polycystic ovary syndrome.
    Endocrine, 2006, Volume: 30, Issue:1

    Topics: Age Factors; Alcohol Drinking; Body Weight; Caffeine; Female; Humans; Hypoglycemic Agents; Infertili

2006
Lifestyle choices, diet, and insulin sensitizers in polycystic ovary syndrome.
    Endocrine, 2006, Volume: 30, Issue:1

    Topics: Age Factors; Alcohol Drinking; Body Weight; Caffeine; Female; Humans; Hypoglycemic Agents; Infertili

2006
Oral antidiabetic drugs: bioavailability assessment of fixed-dose combination tablets of pioglitazone and metformin. Effect of body weight, gender, and race on systemic exposures of each drug.
    Journal of clinical pharmacology, 2007, Volume: 47, Issue:1

    Topics: Administration, Oral; Adult; Area Under Curve; Biological Availability; Black People; Body Weight; D

2007
[Diabetes type 2 in pediatrics: diagnosis and management].
    Revue medicale suisse, 2007, Apr-18, Volume: 3, Issue:107

    Topics: Adolescent; Body Weight; Child; Child, Preschool; Diabetes Complications; Diabetes Mellitus, Type 2;

2007
Metformin and body weight.
    International journal of obesity (2005), 2008, Volume: 32, Issue:1

    Topics: Adolescent; Adult; Body Weight; Child; Diabetes Mellitus, Type 2; Female; Humans; Hypoglycemic Agent

2008
DPP-4 inhibitors.
    Best practice & research. Clinical endocrinology & metabolism, 2007, Volume: 21, Issue:4

    Topics: Adamantane; Animals; Body Weight; Diabetes Mellitus, Type 2; Dipeptidyl-Peptidase IV Inhibitors; Dru

2007
Cardiovascular risk in women with polycystic ovary syndrome.
    Minerva endocrinologica, 2007, Volume: 32, Issue:4

    Topics: Atherosclerosis; Biomarkers; Body Weight; Cardiovascular Diseases; Diabetes Mellitus, Type 2; Exerci

2007
Management of type 2 diabetes in the obese patient: current concerns and emerging therapies.
    Current medical research and opinion, 2008, Volume: 24, Issue:2

    Topics: Anti-Obesity Agents; Body Weight; Diabetes Mellitus, Type 2; Humans; Hypoglycemic Agents; Incretins;

2008
Pharmacotherapy for obesity.
    Current atherosclerosis reports, 2007, Volume: 9, Issue:6

    Topics: Amyloid; Anti-Obesity Agents; Appetite Depressants; Body Weight; Chronic Disease; Comorbidity; Cyclo

2007
Glycaemic control and adverse events in patients with type 2 diabetes treated with metformin + sulphonylurea: a meta-analysis.
    Diabetes, obesity & metabolism, 2008, Volume: 10 Suppl 1

    Topics: Blood Glucose; Body Weight; Diabetes Mellitus, Type 2; Drug Therapy, Combination; Glycated Hemoglobi

2008
Role of metformin for weight management in patients without type 2 diabetes.
    The Annals of pharmacotherapy, 2008, Volume: 42, Issue:6

    Topics: Adolescent; Adult; Anti-Obesity Agents; Body Weight; Clinical Trials as Topic; Humans; Hypoglycemic

2008
[The value of metformin in therapy of type 2 diabetes: effect on insulin resistance, diabetic control and cardiovascular risk factors].
    Wiener klinische Wochenschrift, 1994, Volume: 106, Issue:24

    Topics: Blood Glucose; Body Weight; Clinical Trials as Topic; Diabetes Mellitus, Type 2; Diabetic Angiopathi

1994
Worldwide experience of metformin as an effective glucose-lowering agent: a meta-analysis.
    Diabetes/metabolism reviews, 1995, Volume: 11 Suppl 1

    Topics: Body Weight; Diabetes Mellitus, Type 2; Humans; Hypoglycemic Agents; Metformin

1995
Efficacy of metformin in the treatment of NIDDM. Meta-analysis.
    Diabetes care, 1999, Volume: 22, Issue:1

    Topics: Blood Glucose; Body Weight; Diabetes Mellitus, Type 2; Glycated Hemoglobin; Humans; Hypoglycemic Age

1999
A risk-benefit assessment of metformin in type 2 diabetes mellitus.
    Drug safety, 1999, Volume: 20, Issue:6

    Topics: Acidosis, Lactic; Body Weight; Contraindications; Diabetes Mellitus, Type 2; Female; Glucose; Humans

1999
Should patients with polycystic ovarian syndrome be treated with metformin? A note of cautious optimism.
    Human reproduction (Oxford, England), 2002, Volume: 17, Issue:4

    Topics: Anovulation; Body Weight; Cardiovascular Diseases; Diabetes Mellitus, Type 2; Female; Gastrointestin

2002
Metformin: a review of its pharmacological properties and therapeutic use.
    Diabete & metabolisme, 1979, Volume: 5, Issue:3

    Topics: Animals; Body Weight; Diabetes Mellitus; Gluconeogenesis; Glucose; Glycogen; Humans; Insulin; Insuli

1979
Glucose tolerance tests in the clinical picture of chronic liver diseases.
    Acta Universitatis Carolinae. Medica. Monographia, 1975, Issue:67

    Topics: Adolescent; Adult; Age Factors; Aged; Alanine Transaminase; Aspartate Aminotransferases; Body Weight

1975
[Glycemic equilibrium and weight evolution in diabetics taking metformin].
    Journees annuelles de diabetologie de l'Hotel-Dieu, 1991

    Topics: Blood Glucose; Body Weight; Clinical Trials as Topic; Diabetes Mellitus, Type 2; Humans; Meta-Analys

1991

Trials

266 trials available for metformin and Body Weight

ArticleYear
Metformin maintains intrahepatic triglyceride content through increased hepatic de novo lipogenesis.
    European journal of endocrinology, 2022, Feb-07, Volume: 186, Issue:3

    Topics: Adult; Body Weight; Cohort Studies; Diabetes Mellitus, Type 2; Female; Humans; Hypoglycemic Agents;

2022
Fixed-ratio combination of insulin glargine plus lixisenatide (iGlarLixi) improves ß-cell function in people with type 2 diabetes.
    Diabetes, obesity & metabolism, 2022, Volume: 24, Issue:6

    Topics: Blood Glucose; Body Weight; Diabetes Mellitus, Type 2; Drug Combinations; Glucagon-Like Peptide-1 Re

2022
Effect of once-weekly semaglutide versus thrice-daily insulin aspart, both as add-on to metformin and optimized insulin glargine treatment in participants with type 2 diabetes (SUSTAIN 11): A randomized, open-label, multinational, phase 3b trial.
    Diabetes, obesity & metabolism, 2022, Volume: 24, Issue:9

    Topics: Adult; Blood Glucose; Body Weight; Diabetes Mellitus, Type 2; Drug Therapy, Combination; Glucagon-Li

2022
Efficacy and Safety of Once-Weekly Efpeglenatide Monotherapy Versus Placebo in Type 2 Diabetes: The AMPLITUDE-M Randomized Controlled Trial.
    Diabetes care, 2022, 07-07, Volume: 45, Issue:7

    Topics: Adult; Blood Glucose; Body Weight; Diabetes Mellitus, Type 2; Double-Blind Method; Drug Therapy, Com

2022
Efficacy and safety of janagliflozin as add-on therapy to metformin in Chinese patients with type 2 diabetes inadequately controlled with metformin alone: A multicentre, randomized, double-blind, placebo-controlled, phase 3 trial.
    Diabetes, obesity & metabolism, 2023, Volume: 25, Issue:3

    Topics: Blood Glucose; Body Weight; Cholesterol; Diabetes Mellitus, Type 2; Double-Blind Method; Drug Therap

2023
Efficacy and safety of janagliflozin as add-on therapy to metformin in Chinese patients with type 2 diabetes inadequately controlled with metformin alone: A multicentre, randomized, double-blind, placebo-controlled, phase 3 trial.
    Diabetes, obesity & metabolism, 2023, Volume: 25, Issue:3

    Topics: Blood Glucose; Body Weight; Cholesterol; Diabetes Mellitus, Type 2; Double-Blind Method; Drug Therap

2023
Efficacy and safety of janagliflozin as add-on therapy to metformin in Chinese patients with type 2 diabetes inadequately controlled with metformin alone: A multicentre, randomized, double-blind, placebo-controlled, phase 3 trial.
    Diabetes, obesity & metabolism, 2023, Volume: 25, Issue:3

    Topics: Blood Glucose; Body Weight; Cholesterol; Diabetes Mellitus, Type 2; Double-Blind Method; Drug Therap

2023
Efficacy and safety of janagliflozin as add-on therapy to metformin in Chinese patients with type 2 diabetes inadequately controlled with metformin alone: A multicentre, randomized, double-blind, placebo-controlled, phase 3 trial.
    Diabetes, obesity & metabolism, 2023, Volume: 25, Issue:3

    Topics: Blood Glucose; Body Weight; Cholesterol; Diabetes Mellitus, Type 2; Double-Blind Method; Drug Therap

2023
Efficacy and safety of janagliflozin as add-on therapy to metformin in Chinese patients with type 2 diabetes inadequately controlled with metformin alone: A multicentre, randomized, double-blind, placebo-controlled, phase 3 trial.
    Diabetes, obesity & metabolism, 2023, Volume: 25, Issue:3

    Topics: Blood Glucose; Body Weight; Cholesterol; Diabetes Mellitus, Type 2; Double-Blind Method; Drug Therap

2023
Efficacy and safety of janagliflozin as add-on therapy to metformin in Chinese patients with type 2 diabetes inadequately controlled with metformin alone: A multicentre, randomized, double-blind, placebo-controlled, phase 3 trial.
    Diabetes, obesity & metabolism, 2023, Volume: 25, Issue:3

    Topics: Blood Glucose; Body Weight; Cholesterol; Diabetes Mellitus, Type 2; Double-Blind Method; Drug Therap

2023
Efficacy and safety of janagliflozin as add-on therapy to metformin in Chinese patients with type 2 diabetes inadequately controlled with metformin alone: A multicentre, randomized, double-blind, placebo-controlled, phase 3 trial.
    Diabetes, obesity & metabolism, 2023, Volume: 25, Issue:3

    Topics: Blood Glucose; Body Weight; Cholesterol; Diabetes Mellitus, Type 2; Double-Blind Method; Drug Therap

2023
Efficacy and safety of janagliflozin as add-on therapy to metformin in Chinese patients with type 2 diabetes inadequately controlled with metformin alone: A multicentre, randomized, double-blind, placebo-controlled, phase 3 trial.
    Diabetes, obesity & metabolism, 2023, Volume: 25, Issue:3

    Topics: Blood Glucose; Body Weight; Cholesterol; Diabetes Mellitus, Type 2; Double-Blind Method; Drug Therap

2023
Efficacy and safety of janagliflozin as add-on therapy to metformin in Chinese patients with type 2 diabetes inadequately controlled with metformin alone: A multicentre, randomized, double-blind, placebo-controlled, phase 3 trial.
    Diabetes, obesity & metabolism, 2023, Volume: 25, Issue:3

    Topics: Blood Glucose; Body Weight; Cholesterol; Diabetes Mellitus, Type 2; Double-Blind Method; Drug Therap

2023
Study protocol: Behavioral economics and self-determination theory to change diabetes risk (BEST Change).
    Contemporary clinical trials, 2023, Volume: 124

    Topics: Adult; Body Weight; Diabetes Mellitus, Type 2; Economics, Behavioral; Humans; Metformin; Motivation;

2023
Study protocol: Behavioral economics and self-determination theory to change diabetes risk (BEST Change).
    Contemporary clinical trials, 2023, Volume: 124

    Topics: Adult; Body Weight; Diabetes Mellitus, Type 2; Economics, Behavioral; Humans; Metformin; Motivation;

2023
Study protocol: Behavioral economics and self-determination theory to change diabetes risk (BEST Change).
    Contemporary clinical trials, 2023, Volume: 124

    Topics: Adult; Body Weight; Diabetes Mellitus, Type 2; Economics, Behavioral; Humans; Metformin; Motivation;

2023
Study protocol: Behavioral economics and self-determination theory to change diabetes risk (BEST Change).
    Contemporary clinical trials, 2023, Volume: 124

    Topics: Adult; Body Weight; Diabetes Mellitus, Type 2; Economics, Behavioral; Humans; Metformin; Motivation;

2023
Short-term effect of polyethylene glycol loxenatide on weight loss in overweight or obese patients with type 2 diabetes: An open-label, parallel-arm, randomized, metformin-controlled trial.
    Frontiers in endocrinology, 2023, Volume: 14

    Topics: Body Weight; Diabetes Mellitus, Type 2; Humans; Hypoglycemic Agents; Metformin; Obesity; Overweight;

2023
Effectiveness and safety of Daixie Decoction granules combined with metformin for the treatment of T2DM patients with obesity: study protocol for a randomized, double-blinded, placebo-controlled, multicentre clinical trial.
    Trials, 2023, Apr-19, Volume: 24, Issue:1

    Topics: Body Weight; Diabetes Mellitus, Type 2; Double-Blind Method; Humans; Metformin; Multicenter Studies

2023
Adding empagliflozin to sitagliptin plus metformin vs. adding sitagliptin to empagliflozin plus metformin as triple therapy in Egyptian patients with type 2 diabetes: a 12-week open trial.
    European review for medical and pharmacological sciences, 2023, Volume: 27, Issue:15

    Topics: Blood Glucose; Body Weight; Diabetes Mellitus, Type 2; Egypt; Glycated Hemoglobin; Humans; Metformin

2023
Predictors of ≥15% Weight Reduction and Associated Changes in Cardiometabolic Risk Factors With Tirzepatide in Adults With Type 2 Diabetes in SURPASS 1-4.
    Diabetes care, 2023, Dec-01, Volume: 46, Issue:12

    Topics: Adult; Blood Glucose; Body Weight; Cardiometabolic Risk Factors; Cholesterol; Diabetes Mellitus, Typ

2023
Efficacy, Safety, and Tolerability of Oral Semaglutide Versus Placebo Added to Insulin With or Without Metformin in Patients With Type 2 Diabetes: The PIONEER 8 Trial.
    Diabetes care, 2019, Volume: 42, Issue:12

    Topics: Adult; Body Weight; Diabetes Mellitus, Type 2; Double-Blind Method; Drug Therapy, Combination; Femal

2019
Metformin blunts muscle hypertrophy in response to progressive resistance exercise training in older adults: A randomized, double-blind, placebo-controlled, multicenter trial: The MASTERS trial.
    Aging cell, 2019, Volume: 18, Issue:6

    Topics: Aged; Aged, 80 and over; Body Composition; Body Weight; Cells, Cultured; Double-Blind Method; Exerci

2019
Effects of metformin administration on endocrine-metabolic parameters, visceral adiposity and cardiovascular risk factors in children with obesity and risk markers for metabolic syndrome: A pilot study.
    PloS one, 2019, Volume: 14, Issue:12

    Topics: Adolescent; Body Mass Index; Body Weight; C-Reactive Protein; Carotid Intima-Media Thickness; Child;

2019
GDF15 mediates the effects of metformin on body weight and energy balance.
    Nature, 2020, Volume: 578, Issue:7795

    Topics: Administration, Oral; Adult; Aged; Animals; Blood Glucose; Body Weight; Diet, High-Fat; Double-Blind

2020
Efficacy and safety of dapagliflozin plus saxagliptin versus insulin glargine over 52 weeks as add-on to metformin with or without sulphonylurea in patients with type 2 diabetes: A randomized, parallel-design, open-label, Phase 3 trial.
    Diabetes, obesity & metabolism, 2020, Volume: 22, Issue:6

    Topics: Adamantane; Adult; Benzhydryl Compounds; Blood Glucose; Body Weight; Diabetes Mellitus, Type 2; Dipe

2020
Metformin Lowers Body Weight But Fails to Increase Insulin Sensitivity in Chronic Heart Failure Patients without Diabetes: a Randomized, Double-Blind, Placebo-Controlled Study.
    Cardiovascular drugs and therapy, 2021, Volume: 35, Issue:3

    Topics: Aged; Body Composition; Body Weight; Calorimetry, Indirect; Double-Blind Method; Female; Glucagon; G

2021
Liraglutide or insulin glargine treatments improves hepatic fat in obese patients with type 2 diabetes and nonalcoholic fatty liver disease in twenty-six weeks: A randomized placebo-controlled trial.
    Diabetes research and clinical practice, 2020, Volume: 170

    Topics: Adult; Blood Glucose; Body Weight; China; Diabetes Mellitus, Type 2; Drug Therapy, Combination; Fema

2020
Empagliflozin treatment effects across categories of baseline HbA1c, body weight and blood pressure as an add-on to metformin in patients with type 2 diabetes.
    Diabetes, obesity & metabolism, 2021, Volume: 23, Issue:2

    Topics: Aged; Benzhydryl Compounds; Blood Pressure; Body Weight; Diabetes Mellitus, Type 2; Double-Blind Met

2021
Empagliflozin treatment effects across categories of baseline HbA1c, body weight and blood pressure as an add-on to metformin in patients with type 2 diabetes.
    Diabetes, obesity & metabolism, 2021, Volume: 23, Issue:2

    Topics: Aged; Benzhydryl Compounds; Blood Pressure; Body Weight; Diabetes Mellitus, Type 2; Double-Blind Met

2021
Empagliflozin treatment effects across categories of baseline HbA1c, body weight and blood pressure as an add-on to metformin in patients with type 2 diabetes.
    Diabetes, obesity & metabolism, 2021, Volume: 23, Issue:2

    Topics: Aged; Benzhydryl Compounds; Blood Pressure; Body Weight; Diabetes Mellitus, Type 2; Double-Blind Met

2021
Empagliflozin treatment effects across categories of baseline HbA1c, body weight and blood pressure as an add-on to metformin in patients with type 2 diabetes.
    Diabetes, obesity & metabolism, 2021, Volume: 23, Issue:2

    Topics: Aged; Benzhydryl Compounds; Blood Pressure; Body Weight; Diabetes Mellitus, Type 2; Double-Blind Met

2021
Liraglutide and sitagliptin have no effect on intestinal microbiota composition: A 12-week randomized placebo-controlled trial in adults with type 2 diabetes.
    Diabetes & metabolism, 2021, Volume: 47, Issue:5

    Topics: Adult; Aged; Bile Acids and Salts; Body Weight; Diabetes Mellitus, Type 2; Dipeptidyl-Peptidase IV I

2021
Dapagliflozin increases the lean-to total mass ratio in type 2 diabetes mellitus.
    Nutrition & diabetes, 2021, 06-12, Volume: 11, Issue:1

    Topics: Absorptiometry, Photon; Adult; Aged; Benzhydryl Compounds; Blood Glucose; Body Composition; Body Wei

2021
Danuglipron (PF-06882961) in type 2 diabetes: a randomized, placebo-controlled, multiple ascending-dose phase 1 trial.
    Nature medicine, 2021, Volume: 27, Issue:6

    Topics: Animals; Blood Glucose; Body Weight; Diabetes Mellitus, Type 2; Female; Glucagon-Like Peptide-1 Rece

2021
A 24-month metformin treatment study of children with obesity: Changes in circulating GDF-15 and associations with changes in body weight and visceral fat.
    Pediatric obesity, 2022, Volume: 17, Issue:2

    Topics: Body Mass Index; Body Weight; Child; Double-Blind Method; Growth Differentiation Factor 15; Humans;

2022
Protocol for a randomised controlled trial of the effect of dapagliflozin, metformin and exercise on glycaemic variability, body composition and cardiovascular risk in prediabetes (the PRE-D Trial).
    BMJ open, 2017, 06-06, Volume: 7, Issue:5

    Topics: Adult; Aged; Benzhydryl Compounds; Body Composition; Body Weight; Cardiovascular Diseases; Denmark;

2017
Protocol for a randomised controlled trial of the effect of dapagliflozin, metformin and exercise on glycaemic variability, body composition and cardiovascular risk in prediabetes (the PRE-D Trial).
    BMJ open, 2017, 06-06, Volume: 7, Issue:5

    Topics: Adult; Aged; Benzhydryl Compounds; Body Composition; Body Weight; Cardiovascular Diseases; Denmark;

2017
Protocol for a randomised controlled trial of the effect of dapagliflozin, metformin and exercise on glycaemic variability, body composition and cardiovascular risk in prediabetes (the PRE-D Trial).
    BMJ open, 2017, 06-06, Volume: 7, Issue:5

    Topics: Adult; Aged; Benzhydryl Compounds; Body Composition; Body Weight; Cardiovascular Diseases; Denmark;

2017
Protocol for a randomised controlled trial of the effect of dapagliflozin, metformin and exercise on glycaemic variability, body composition and cardiovascular risk in prediabetes (the PRE-D Trial).
    BMJ open, 2017, 06-06, Volume: 7, Issue:5

    Topics: Adult; Aged; Benzhydryl Compounds; Body Composition; Body Weight; Cardiovascular Diseases; Denmark;

2017
Patient-reported Outcomes in Patients with Type 2 Diabetes Treated with Dulaglutide Added to Titrated Insulin Glargine (AWARD-9).
    Clinical therapeutics, 2017, Volume: 39, Issue:11

    Topics: Aged; Blood Glucose; Body Weight; Diabetes Mellitus, Type 2; Double-Blind Method; Female; Glucagon-L

2017
Safety and efficacy of metformin up-titration in Japanese patients with type 2 diabetes mellitus treated with vildagliptin and low-dose metformin.
    Expert opinion on pharmacotherapy, 2017, Volume: 18, Issue:18

    Topics: Adamantane; Aged; Blood Glucose; Body Weight; Diabetes Mellitus, Type 2; Drug Therapy, Combination;

2017
Effects of exenatide once weekly plus dapagliflozin, exenatide once weekly, or dapagliflozin, added to metformin monotherapy, on body weight, systolic blood pressure, and triglycerides in patients with type 2 diabetes in the DURATION-8 study.
    Diabetes, obesity & metabolism, 2018, Volume: 20, Issue:6

    Topics: Anti-Obesity Agents; Benzhydryl Compounds; Blood Pressure; Body Mass Index; Body Weight; Diabetes Me

2018
CoMET: a protocol for a randomised controlled trial of co-commencement of METformin as an adjunctive treatment to attenuate weight gain and metabolic syndrome in patients with schizophrenia newly commenced on clozapine.
    BMJ open, 2018, 03-02, Volume: 8, Issue:3

    Topics: Antipsychotic Agents; Body Mass Index; Body Weight; Clozapine; Diabetes Mellitus, Type 2; Double-Bli

2018
Effects of exenatide once weekly plus dapagliflozin, exenatide once weekly alone, or dapagliflozin alone added to metformin monotherapy in subgroups of patients with type 2 diabetes in the DURATION-8 randomized controlled trial.
    Diabetes, obesity & metabolism, 2018, Volume: 20, Issue:6

    Topics: Administration, Oral; Adult; Aged; Benzhydryl Compounds; Body Weight; Diabetes Mellitus, Type 2; Dru

2018
Efficacy and safety of Sancai powder in patients with type 2 diabetes mellitus: a randomized controlled trial.
    Journal of traditional Chinese medicine = Chung i tsa chih ying wen pan, 2016, Volume: 36, Issue:5

    Topics: Adult; Aged; Blood Glucose; Body Weight; Diabetes Mellitus, Type 2; Drugs, Chinese Herbal; Female; G

2016
High-Dose, Diazoxide-Mediated Insulin Suppression Boosts Weight Loss Induced by Lifestyle Intervention.
    The Journal of clinical endocrinology and metabolism, 2018, 11-01, Volume: 103, Issue:11

    Topics: Adult; Blood Glucose; Body Mass Index; Body Weight; Diazoxide; Dose-Response Relationship, Drug; Dou

2018
Dapagliflozin versus saxagliptin as add-on therapy in patients with type 2 diabetes inadequately controlled with metformin.
    Archives of endocrinology and metabolism, 2018, Volume: 62, Issue:4

    Topics: Adamantane; Benzhydryl Compounds; Blood Glucose; Blood Pressure; Body Weight; Diabetes Mellitus, Typ

2018
Liraglutide, Sitagliptin, and Insulin Glargine Added to Metformin: The Effect on Body Weight and Intrahepatic Lipid in Patients With Type 2 Diabetes Mellitus and Nonalcoholic Fatty Liver Disease.
    Hepatology (Baltimore, Md.), 2019, Volume: 69, Issue:6

    Topics: Adult; Aged; Blood Glucose; Body Weight; Comorbidity; Diabetes Mellitus, Type 2; Dose-Response Relat

2019
A whey/guar "preload" improves postprandial glycaemia and glycated haemoglobin levels in type 2 diabetes: A 12-week, single-blind, randomized, placebo-controlled trial.
    Diabetes, obesity & metabolism, 2019, Volume: 21, Issue:4

    Topics: Aged; Blood Glucose; Body Composition; Body Weight; Diabetes Mellitus, Type 2; Diet, Diabetic; Energ

2019
Comparative effect of saxagliptin and glimepiride with a composite endpoint of adequate glycaemic control without hypoglycaemia and without weight gain in patients uncontrolled with metformin therapy: Results from the SPECIFY study, a 48-week, multi-centr
    Diabetes, obesity & metabolism, 2019, Volume: 21, Issue:4

    Topics: Adamantane; Adult; Aged; Blood Glucose; Body Weight; Diabetes Mellitus, Type 2; Dipeptides; Female;

2019
Randomized Controlled Trial of a Leucine-Metformin-Sildenafil Combination (NS-0200) on Weight and Metabolic Parameters.
    Obesity (Silver Spring, Md.), 2019, Volume: 27, Issue:1

    Topics: Body Weight; Double-Blind Method; Female; Humans; Hypoglycemic Agents; Leucine; Male; Metformin; Mid

2019
Effect of intensive lifestyle modification & metformin on cardiovascular risk in prediabetes: A pilot randomized control trial.
    The Indian journal of medical research, 2018, Volume: 148, Issue:6

    Topics: Adult; Blood Glucose; Body Weight; C-Reactive Protein; Cardiovascular Diseases; Carotid Intima-Media

2018
A randomized controlled trial of metformin on left ventricular hypertrophy in patients with coronary artery disease without diabetes: the MET-REMODEL trial.
    European heart journal, 2019, 11-01, Volume: 40, Issue:41

    Topics: Aged; Body Weight; Coronary Artery Disease; Female; Heart Ventricles; Humans; Hypertrophy, Left Vent

2019
Triple therapy with low-dose dapagliflozin plus saxagliptin versus dual therapy with each monocomponent, all added to metformin, in uncontrolled type 2 diabetes.
    Diabetes, obesity & metabolism, 2019, Volume: 21, Issue:9

    Topics: Adamantane; Benzhydryl Compounds; Blood Glucose; Body Weight; Diabetes Mellitus, Type 2; Dipeptides;

2019
Effect of Nigella Sativa oil versus metformin on glycemic control and biochemical parameters of newly diagnosed type 2 diabetes mellitus patients.
    Endocrine, 2019, Volume: 65, Issue:2

    Topics: Blood Glucose; Body Weight; Diabetes Mellitus, Type 2; Female; Humans; Hypoglycemic Agents; Male; Me

2019
Once-daily initiation of basal insulin as add-on to metformin: a 26-week, randomized, treat-to-target trial comparing insulin detemir with insulin glargine in patients with type 2 diabetes.
    Diabetes, obesity & metabolism, 2013, Volume: 15, Issue:8

    Topics: Argentina; Blood Glucose; Body Mass Index; Body Weight; Diabetes Mellitus, Type 2; Drug Administrati

2013
Sitagliptin as add-on therapy in insulin deficiency: biomarkers of therapeutic efficacy respond differently in type 1 and type 2 diabetes.
    Drug design, development and therapy, 2013, Volume: 7

    Topics: Adult; Aged; Biomarkers; Blood Glucose; Body Weight; Cholesterol, LDL; Diabetes Mellitus, Type 1; Di

2013
Impact of baseline BMI on glycemic control and weight change with metformin monotherapy in Chinese type 2 diabetes patients: phase IV open-label trial.
    PloS one, 2013, Volume: 8, Issue:2

    Topics: Adult; Blood Glucose; Body Mass Index; Body Weight; Diabetes Mellitus, Type 2; Female; Glycated Hemo

2013
Ultrasonography modifications of visceral and subcutaneous adipose tissue after pioglitazone or glibenclamide therapy combined with rosuvastatin in type 2 diabetic patients not well controlled by metformin.
    European journal of gastroenterology & hepatology, 2013, Volume: 25, Issue:9

    Topics: Adipokines; Aged; Biomarkers; Blood Glucose; Body Mass Index; Body Weight; Diabetes Mellitus, Type 2

2013
[Long-term efficacy of dapagliflozin in patients with type 2 diabetes mellitus receiving high doses of insulin].
    Deutsche medizinische Wochenschrift (1946), 2013, Volume: 138 Suppl 1

    Topics: Aged; Benzhydryl Compounds; Blood Glucose; Body Weight; Diabetes Mellitus, Type 2; Dose-Response Rel

2013
[Dapagliflozin versus glipizide as add-on therapy in patients with type 2 diabetes who have inadequate glycemic control with metformin].
    Deutsche medizinische Wochenschrift (1946), 2013, Volume: 138 Suppl 1

    Topics: Aged; Balanitis; Benzhydryl Compounds; Blood Glucose; Body Weight; Candidiasis, Vulvovaginal; Diabet

2013
Randomized trial of continuous subcutaneous delivery of exenatide by ITCA 650 versus twice-daily exenatide injections in metformin-treated type 2 diabetes.
    Diabetes care, 2013, Volume: 36, Issue:9

    Topics: Adolescent; Adult; Aged; Blood Glucose; Body Weight; Diabetes Mellitus, Type 2; Exenatide; Humans; H

2013
Impact of diagnosis of diabetes on health-related quality of life among high risk individuals: the Diabetes Prevention Program outcomes study.
    Quality of life research : an international journal of quality of life aspects of treatment, care and rehabilitation, 2014, Volume: 23, Issue:1

    Topics: Body Mass Index; Body Weight; Cohort Studies; Diabetes Mellitus, Type 2; Female; Follow-Up Studies;

2014
Impact of diagnosis of diabetes on health-related quality of life among high risk individuals: the Diabetes Prevention Program outcomes study.
    Quality of life research : an international journal of quality of life aspects of treatment, care and rehabilitation, 2014, Volume: 23, Issue:1

    Topics: Body Mass Index; Body Weight; Cohort Studies; Diabetes Mellitus, Type 2; Female; Follow-Up Studies;

2014
Impact of diagnosis of diabetes on health-related quality of life among high risk individuals: the Diabetes Prevention Program outcomes study.
    Quality of life research : an international journal of quality of life aspects of treatment, care and rehabilitation, 2014, Volume: 23, Issue:1

    Topics: Body Mass Index; Body Weight; Cohort Studies; Diabetes Mellitus, Type 2; Female; Follow-Up Studies;

2014
Impact of diagnosis of diabetes on health-related quality of life among high risk individuals: the Diabetes Prevention Program outcomes study.
    Quality of life research : an international journal of quality of life aspects of treatment, care and rehabilitation, 2014, Volume: 23, Issue:1

    Topics: Body Mass Index; Body Weight; Cohort Studies; Diabetes Mellitus, Type 2; Female; Follow-Up Studies;

2014
Variation in inflammatory markers and glycemic parameters after 12 months of exenatide plus metformin treatment compared with metformin alone: a randomized placebo-controlled trial.
    Pharmacotherapy, 2013, Volume: 33, Issue:8

    Topics: Aged; Arginine; Biomarkers; Blood Glucose; Body Mass Index; Body Weight; C-Peptide; Chimerin Protein

2013
Effects of adjunctive metformin on metabolic traits in nondiabetic clozapine-treated patients with schizophrenia and the effect of metformin discontinuation on body weight: a 24-week, randomized, double-blind, placebo-controlled study.
    The Journal of clinical psychiatry, 2013, Volume: 74, Issue:5

    Topics: Adult; Body Weight; Clozapine; Double-Blind Method; Female; Follow-Up Studies; Humans; Male; Metabol

2013
Empagliflozin improves glycaemic and weight control as add-on therapy to pioglitazone or pioglitazone plus metformin in patients with type 2 diabetes: a 24-week, randomized, placebo-controlled trial.
    Diabetes, obesity & metabolism, 2014, Volume: 16, Issue:2

    Topics: Aged; Benzhydryl Compounds; Blood Glucose; Body Weight; Diabetes Mellitus, Type 2; Double-Blind Meth

2014
Empagliflozin as add-on to metformin plus sulfonylurea in patients with type 2 diabetes: a 24-week, randomized, double-blind, placebo-controlled trial.
    Diabetes care, 2013, Volume: 36, Issue:11

    Topics: Adult; Aged; Benzhydryl Compounds; Blood Glucose; Blood Pressure; Body Weight; Diabetes Mellitus, Ty

2013
Empagliflozin as add-on to metformin plus sulfonylurea in patients with type 2 diabetes: a 24-week, randomized, double-blind, placebo-controlled trial.
    Diabetes care, 2013, Volume: 36, Issue:11

    Topics: Adult; Aged; Benzhydryl Compounds; Blood Glucose; Blood Pressure; Body Weight; Diabetes Mellitus, Ty

2013
Empagliflozin as add-on to metformin plus sulfonylurea in patients with type 2 diabetes: a 24-week, randomized, double-blind, placebo-controlled trial.
    Diabetes care, 2013, Volume: 36, Issue:11

    Topics: Adult; Aged; Benzhydryl Compounds; Blood Glucose; Blood Pressure; Body Weight; Diabetes Mellitus, Ty

2013
Empagliflozin as add-on to metformin plus sulfonylurea in patients with type 2 diabetes: a 24-week, randomized, double-blind, placebo-controlled trial.
    Diabetes care, 2013, Volume: 36, Issue:11

    Topics: Adult; Aged; Benzhydryl Compounds; Blood Glucose; Blood Pressure; Body Weight; Diabetes Mellitus, Ty

2013
Acarbose plus metformin fixed-dose combination outperforms acarbose monotherapy for type 2 diabetes.
    Diabetes research and clinical practice, 2013, Volume: 102, Issue:1

    Topics: Acarbose; Adult; Aged; Blood Glucose; Body Weight; Diabetes Mellitus, Type 2; Drug Combinations; Fem

2013
Efficacy and safety of canagliflozin compared with placebo and sitagliptin in patients with type 2 diabetes on background metformin monotherapy: a randomised trial.
    Diabetologia, 2013, Volume: 56, Issue:12

    Topics: Adolescent; Aged; Aged, 80 and over; Blood Glucose; Blood Pressure; Body Weight; Canagliflozin; Diab

2013
Efficacy and safety of canagliflozin compared with placebo and sitagliptin in patients with type 2 diabetes on background metformin monotherapy: a randomised trial.
    Diabetologia, 2013, Volume: 56, Issue:12

    Topics: Adolescent; Aged; Aged, 80 and over; Blood Glucose; Blood Pressure; Body Weight; Canagliflozin; Diab

2013
Efficacy and safety of canagliflozin compared with placebo and sitagliptin in patients with type 2 diabetes on background metformin monotherapy: a randomised trial.
    Diabetologia, 2013, Volume: 56, Issue:12

    Topics: Adolescent; Aged; Aged, 80 and over; Blood Glucose; Blood Pressure; Body Weight; Canagliflozin; Diab

2013
Efficacy and safety of canagliflozin compared with placebo and sitagliptin in patients with type 2 diabetes on background metformin monotherapy: a randomised trial.
    Diabetologia, 2013, Volume: 56, Issue:12

    Topics: Adolescent; Aged; Aged, 80 and over; Blood Glucose; Blood Pressure; Body Weight; Canagliflozin; Diab

2013
[A combination of dipeptidyl peptidase-4 inhibitor and metformin in the treatment of patients with type 2 diabetes mellitus: effective control of glycemia, weight, and quantitative body composition].
    Terapevticheskii arkhiv, 2013, Volume: 85, Issue:8

    Topics: Absorptiometry, Photon; Adamantane; Blood Glucose; Body Composition; Body Mass Index; Body Weight; D

2013
Dapagliflozin is effective as add-on therapy to sitagliptin with or without metformin: a 24-week, multicenter, randomized, double-blind, placebo-controlled study.
    Diabetes care, 2014, Volume: 37, Issue:3

    Topics: Benzhydryl Compounds; Blood Glucose; Blood Pressure; Body Weight; Diabetes Mellitus, Type 2; Double-

2014
Dapagliflozin is effective as add-on therapy to sitagliptin with or without metformin: a 24-week, multicenter, randomized, double-blind, placebo-controlled study.
    Diabetes care, 2014, Volume: 37, Issue:3

    Topics: Benzhydryl Compounds; Blood Glucose; Blood Pressure; Body Weight; Diabetes Mellitus, Type 2; Double-

2014
Dapagliflozin is effective as add-on therapy to sitagliptin with or without metformin: a 24-week, multicenter, randomized, double-blind, placebo-controlled study.
    Diabetes care, 2014, Volume: 37, Issue:3

    Topics: Benzhydryl Compounds; Blood Glucose; Blood Pressure; Body Weight; Diabetes Mellitus, Type 2; Double-

2014
Dapagliflozin is effective as add-on therapy to sitagliptin with or without metformin: a 24-week, multicenter, randomized, double-blind, placebo-controlled study.
    Diabetes care, 2014, Volume: 37, Issue:3

    Topics: Benzhydryl Compounds; Blood Glucose; Blood Pressure; Body Weight; Diabetes Mellitus, Type 2; Double-

2014
Dapagliflozin is effective as add-on therapy to sitagliptin with or without metformin: a 24-week, multicenter, randomized, double-blind, placebo-controlled study.
    Diabetes care, 2014, Volume: 37, Issue:3

    Topics: Benzhydryl Compounds; Blood Glucose; Blood Pressure; Body Weight; Diabetes Mellitus, Type 2; Double-

2014
Dapagliflozin is effective as add-on therapy to sitagliptin with or without metformin: a 24-week, multicenter, randomized, double-blind, placebo-controlled study.
    Diabetes care, 2014, Volume: 37, Issue:3

    Topics: Benzhydryl Compounds; Blood Glucose; Blood Pressure; Body Weight; Diabetes Mellitus, Type 2; Double-

2014
Dapagliflozin is effective as add-on therapy to sitagliptin with or without metformin: a 24-week, multicenter, randomized, double-blind, placebo-controlled study.
    Diabetes care, 2014, Volume: 37, Issue:3

    Topics: Benzhydryl Compounds; Blood Glucose; Blood Pressure; Body Weight; Diabetes Mellitus, Type 2; Double-

2014
Dapagliflozin is effective as add-on therapy to sitagliptin with or without metformin: a 24-week, multicenter, randomized, double-blind, placebo-controlled study.
    Diabetes care, 2014, Volume: 37, Issue:3

    Topics: Benzhydryl Compounds; Blood Glucose; Blood Pressure; Body Weight; Diabetes Mellitus, Type 2; Double-

2014
Dapagliflozin is effective as add-on therapy to sitagliptin with or without metformin: a 24-week, multicenter, randomized, double-blind, placebo-controlled study.
    Diabetes care, 2014, Volume: 37, Issue:3

    Topics: Benzhydryl Compounds; Blood Glucose; Blood Pressure; Body Weight; Diabetes Mellitus, Type 2; Double-

2014
Dapagliflozin is effective as add-on therapy to sitagliptin with or without metformin: a 24-week, multicenter, randomized, double-blind, placebo-controlled study.
    Diabetes care, 2014, Volume: 37, Issue:3

    Topics: Benzhydryl Compounds; Blood Glucose; Blood Pressure; Body Weight; Diabetes Mellitus, Type 2; Double-

2014
Dapagliflozin is effective as add-on therapy to sitagliptin with or without metformin: a 24-week, multicenter, randomized, double-blind, placebo-controlled study.
    Diabetes care, 2014, Volume: 37, Issue:3

    Topics: Benzhydryl Compounds; Blood Glucose; Blood Pressure; Body Weight; Diabetes Mellitus, Type 2; Double-

2014
Dapagliflozin is effective as add-on therapy to sitagliptin with or without metformin: a 24-week, multicenter, randomized, double-blind, placebo-controlled study.
    Diabetes care, 2014, Volume: 37, Issue:3

    Topics: Benzhydryl Compounds; Blood Glucose; Blood Pressure; Body Weight; Diabetes Mellitus, Type 2; Double-

2014
Dapagliflozin is effective as add-on therapy to sitagliptin with or without metformin: a 24-week, multicenter, randomized, double-blind, placebo-controlled study.
    Diabetes care, 2014, Volume: 37, Issue:3

    Topics: Benzhydryl Compounds; Blood Glucose; Blood Pressure; Body Weight; Diabetes Mellitus, Type 2; Double-

2014
Dapagliflozin is effective as add-on therapy to sitagliptin with or without metformin: a 24-week, multicenter, randomized, double-blind, placebo-controlled study.
    Diabetes care, 2014, Volume: 37, Issue:3

    Topics: Benzhydryl Compounds; Blood Glucose; Blood Pressure; Body Weight; Diabetes Mellitus, Type 2; Double-

2014
Dapagliflozin is effective as add-on therapy to sitagliptin with or without metformin: a 24-week, multicenter, randomized, double-blind, placebo-controlled study.
    Diabetes care, 2014, Volume: 37, Issue:3

    Topics: Benzhydryl Compounds; Blood Glucose; Blood Pressure; Body Weight; Diabetes Mellitus, Type 2; Double-

2014
Dapagliflozin is effective as add-on therapy to sitagliptin with or without metformin: a 24-week, multicenter, randomized, double-blind, placebo-controlled study.
    Diabetes care, 2014, Volume: 37, Issue:3

    Topics: Benzhydryl Compounds; Blood Glucose; Blood Pressure; Body Weight; Diabetes Mellitus, Type 2; Double-

2014
Efficacy and safety of vildagliptin in patients with type 2 diabetes mellitus inadequately controlled with dual combination of metformin and sulphonylurea.
    Diabetes, obesity & metabolism, 2014, Volume: 16, Issue:5

    Topics: Adamantane; Adolescent; Adult; Aged; Aged, 80 and over; Blood Glucose; Body Weight; Diabetes Mellitu

2014
Efficacy and safety of vildagliptin in patients with type 2 diabetes mellitus inadequately controlled with dual combination of metformin and sulphonylurea.
    Diabetes, obesity & metabolism, 2014, Volume: 16, Issue:5

    Topics: Adamantane; Adolescent; Adult; Aged; Aged, 80 and over; Blood Glucose; Body Weight; Diabetes Mellitu

2014
Efficacy and safety of vildagliptin in patients with type 2 diabetes mellitus inadequately controlled with dual combination of metformin and sulphonylurea.
    Diabetes, obesity & metabolism, 2014, Volume: 16, Issue:5

    Topics: Adamantane; Adolescent; Adult; Aged; Aged, 80 and over; Blood Glucose; Body Weight; Diabetes Mellitu

2014
Efficacy and safety of vildagliptin in patients with type 2 diabetes mellitus inadequately controlled with dual combination of metformin and sulphonylurea.
    Diabetes, obesity & metabolism, 2014, Volume: 16, Issue:5

    Topics: Adamantane; Adolescent; Adult; Aged; Aged, 80 and over; Blood Glucose; Body Weight; Diabetes Mellitu

2014
A randomized controlled trial of the efficacy and safety of saxagliptin as add-on therapy in patients with type 2 diabetes and inadequate glycaemic control on metformin plus a sulphonylurea.
    Diabetes, obesity & metabolism, 2014, Volume: 16, Issue:5

    Topics: Adamantane; Adult; Australia; Blood Glucose; Body Mass Index; Body Weight; Canada; Diabetes Mellitus

2014
Dose response of continuous subcutaneous infusion of recombinant glucagon-like peptide-1 in combination with metformin and sulphonylurea over 12 weeks in patients with type 2 diabetes mellitus.
    Diabetes, obesity & metabolism, 2014, Volume: 16, Issue:5

    Topics: Adult; Aged; Aged, 80 and over; Analysis of Variance; Blood Glucose; Body Weight; Diabetes Mellitus,

2014
Short-term combined treatment with liraglutide and metformin leads to significant weight loss in obese women with polycystic ovary syndrome and previous poor response to metformin.
    European journal of endocrinology, 2014, Volume: 170, Issue:3

    Topics: Adult; Body Weight; Female; Glucagon-Like Peptide 1; Glucagon-Like Peptide-1 Receptor; Humans; Lirag

2014
Short-term combined treatment with liraglutide and metformin leads to significant weight loss in obese women with polycystic ovary syndrome and previous poor response to metformin.
    European journal of endocrinology, 2014, Volume: 170, Issue:3

    Topics: Adult; Body Weight; Female; Glucagon-Like Peptide 1; Glucagon-Like Peptide-1 Receptor; Humans; Lirag

2014
Short-term combined treatment with liraglutide and metformin leads to significant weight loss in obese women with polycystic ovary syndrome and previous poor response to metformin.
    European journal of endocrinology, 2014, Volume: 170, Issue:3

    Topics: Adult; Body Weight; Female; Glucagon-Like Peptide 1; Glucagon-Like Peptide-1 Receptor; Humans; Lirag

2014
Short-term combined treatment with liraglutide and metformin leads to significant weight loss in obese women with polycystic ovary syndrome and previous poor response to metformin.
    European journal of endocrinology, 2014, Volume: 170, Issue:3

    Topics: Adult; Body Weight; Female; Glucagon-Like Peptide 1; Glucagon-Like Peptide-1 Receptor; Humans; Lirag

2014
Short-term combined treatment with liraglutide and metformin leads to significant weight loss in obese women with polycystic ovary syndrome and previous poor response to metformin.
    European journal of endocrinology, 2014, Volume: 170, Issue:3

    Topics: Adult; Body Weight; Female; Glucagon-Like Peptide 1; Glucagon-Like Peptide-1 Receptor; Humans; Lirag

2014
Short-term combined treatment with liraglutide and metformin leads to significant weight loss in obese women with polycystic ovary syndrome and previous poor response to metformin.
    European journal of endocrinology, 2014, Volume: 170, Issue:3

    Topics: Adult; Body Weight; Female; Glucagon-Like Peptide 1; Glucagon-Like Peptide-1 Receptor; Humans; Lirag

2014
Short-term combined treatment with liraglutide and metformin leads to significant weight loss in obese women with polycystic ovary syndrome and previous poor response to metformin.
    European journal of endocrinology, 2014, Volume: 170, Issue:3

    Topics: Adult; Body Weight; Female; Glucagon-Like Peptide 1; Glucagon-Like Peptide-1 Receptor; Humans; Lirag

2014
Short-term combined treatment with liraglutide and metformin leads to significant weight loss in obese women with polycystic ovary syndrome and previous poor response to metformin.
    European journal of endocrinology, 2014, Volume: 170, Issue:3

    Topics: Adult; Body Weight; Female; Glucagon-Like Peptide 1; Glucagon-Like Peptide-1 Receptor; Humans; Lirag

2014
Short-term combined treatment with liraglutide and metformin leads to significant weight loss in obese women with polycystic ovary syndrome and previous poor response to metformin.
    European journal of endocrinology, 2014, Volume: 170, Issue:3

    Topics: Adult; Body Weight; Female; Glucagon-Like Peptide 1; Glucagon-Like Peptide-1 Receptor; Humans; Lirag

2014
Short-term combined treatment with liraglutide and metformin leads to significant weight loss in obese women with polycystic ovary syndrome and previous poor response to metformin.
    European journal of endocrinology, 2014, Volume: 170, Issue:3

    Topics: Adult; Body Weight; Female; Glucagon-Like Peptide 1; Glucagon-Like Peptide-1 Receptor; Humans; Lirag

2014
Short-term combined treatment with liraglutide and metformin leads to significant weight loss in obese women with polycystic ovary syndrome and previous poor response to metformin.
    European journal of endocrinology, 2014, Volume: 170, Issue:3

    Topics: Adult; Body Weight; Female; Glucagon-Like Peptide 1; Glucagon-Like Peptide-1 Receptor; Humans; Lirag

2014
Short-term combined treatment with liraglutide and metformin leads to significant weight loss in obese women with polycystic ovary syndrome and previous poor response to metformin.
    European journal of endocrinology, 2014, Volume: 170, Issue:3

    Topics: Adult; Body Weight; Female; Glucagon-Like Peptide 1; Glucagon-Like Peptide-1 Receptor; Humans; Lirag

2014
Short-term combined treatment with liraglutide and metformin leads to significant weight loss in obese women with polycystic ovary syndrome and previous poor response to metformin.
    European journal of endocrinology, 2014, Volume: 170, Issue:3

    Topics: Adult; Body Weight; Female; Glucagon-Like Peptide 1; Glucagon-Like Peptide-1 Receptor; Humans; Lirag

2014
Short-term combined treatment with liraglutide and metformin leads to significant weight loss in obese women with polycystic ovary syndrome and previous poor response to metformin.
    European journal of endocrinology, 2014, Volume: 170, Issue:3

    Topics: Adult; Body Weight; Female; Glucagon-Like Peptide 1; Glucagon-Like Peptide-1 Receptor; Humans; Lirag

2014
Short-term combined treatment with liraglutide and metformin leads to significant weight loss in obese women with polycystic ovary syndrome and previous poor response to metformin.
    European journal of endocrinology, 2014, Volume: 170, Issue:3

    Topics: Adult; Body Weight; Female; Glucagon-Like Peptide 1; Glucagon-Like Peptide-1 Receptor; Humans; Lirag

2014
Short-term combined treatment with liraglutide and metformin leads to significant weight loss in obese women with polycystic ovary syndrome and previous poor response to metformin.
    European journal of endocrinology, 2014, Volume: 170, Issue:3

    Topics: Adult; Body Weight; Female; Glucagon-Like Peptide 1; Glucagon-Like Peptide-1 Receptor; Humans; Lirag

2014
Short-term combined treatment with liraglutide and metformin leads to significant weight loss in obese women with polycystic ovary syndrome and previous poor response to metformin.
    European journal of endocrinology, 2014, Volume: 170, Issue:3

    Topics: Adult; Body Weight; Female; Glucagon-Like Peptide 1; Glucagon-Like Peptide-1 Receptor; Humans; Lirag

2014
Short-term combined treatment with liraglutide and metformin leads to significant weight loss in obese women with polycystic ovary syndrome and previous poor response to metformin.
    European journal of endocrinology, 2014, Volume: 170, Issue:3

    Topics: Adult; Body Weight; Female; Glucagon-Like Peptide 1; Glucagon-Like Peptide-1 Receptor; Humans; Lirag

2014
Short-term combined treatment with liraglutide and metformin leads to significant weight loss in obese women with polycystic ovary syndrome and previous poor response to metformin.
    European journal of endocrinology, 2014, Volume: 170, Issue:3

    Topics: Adult; Body Weight; Female; Glucagon-Like Peptide 1; Glucagon-Like Peptide-1 Receptor; Humans; Lirag

2014
Short-term combined treatment with liraglutide and metformin leads to significant weight loss in obese women with polycystic ovary syndrome and previous poor response to metformin.
    European journal of endocrinology, 2014, Volume: 170, Issue:3

    Topics: Adult; Body Weight; Female; Glucagon-Like Peptide 1; Glucagon-Like Peptide-1 Receptor; Humans; Lirag

2014
Short-term combined treatment with liraglutide and metformin leads to significant weight loss in obese women with polycystic ovary syndrome and previous poor response to metformin.
    European journal of endocrinology, 2014, Volume: 170, Issue:3

    Topics: Adult; Body Weight; Female; Glucagon-Like Peptide 1; Glucagon-Like Peptide-1 Receptor; Humans; Lirag

2014
Short-term combined treatment with liraglutide and metformin leads to significant weight loss in obese women with polycystic ovary syndrome and previous poor response to metformin.
    European journal of endocrinology, 2014, Volume: 170, Issue:3

    Topics: Adult; Body Weight; Female; Glucagon-Like Peptide 1; Glucagon-Like Peptide-1 Receptor; Humans; Lirag

2014
Short-term combined treatment with liraglutide and metformin leads to significant weight loss in obese women with polycystic ovary syndrome and previous poor response to metformin.
    European journal of endocrinology, 2014, Volume: 170, Issue:3

    Topics: Adult; Body Weight; Female; Glucagon-Like Peptide 1; Glucagon-Like Peptide-1 Receptor; Humans; Lirag

2014
Short-term combined treatment with liraglutide and metformin leads to significant weight loss in obese women with polycystic ovary syndrome and previous poor response to metformin.
    European journal of endocrinology, 2014, Volume: 170, Issue:3

    Topics: Adult; Body Weight; Female; Glucagon-Like Peptide 1; Glucagon-Like Peptide-1 Receptor; Humans; Lirag

2014
Short-term combined treatment with liraglutide and metformin leads to significant weight loss in obese women with polycystic ovary syndrome and previous poor response to metformin.
    European journal of endocrinology, 2014, Volume: 170, Issue:3

    Topics: Adult; Body Weight; Female; Glucagon-Like Peptide 1; Glucagon-Like Peptide-1 Receptor; Humans; Lirag

2014
Urinary tract infection in randomized phase III studies of canagliflozin, a sodium glucose co-transporter 2 inhibitor.
    Postgraduate medicine, 2014, Volume: 126, Issue:1

    Topics: Adolescent; Adult; Aged; Aged, 80 and over; Blood Glucose; Blood Pressure; Body Weight; Canagliflozi

2014
Efficacy and safety of initial combination therapy with alogliptin plus metformin versus either as monotherapy in drug-naïve patients with type 2 diabetes: a randomized, double-blind, 6-month study.
    Diabetes, obesity & metabolism, 2014, Volume: 16, Issue:7

    Topics: Blood Glucose; Body Weight; Diabetes Mellitus, Type 2; Double-Blind Method; Drug Therapy, Combinatio

2014
Exenatide improves type 2 diabetes concomitant with non-alcoholic fatty liver disease.
    Arquivos brasileiros de endocrinologia e metabologia, 2013, Volume: 57, Issue:9

    Topics: Adiponectin; Adult; Aged; Alanine Transaminase; Blood Glucose; Body Mass Index; Body Weight; C-React

2013
Dapagliflozin improves muscle insulin sensitivity but enhances endogenous glucose production.
    The Journal of clinical investigation, 2014, Volume: 124, Issue:2

    Topics: Benzhydryl Compounds; Blood Glucose; Body Weight; Diabetes Mellitus, Type 2; Fasting; Glucagon; Gluc

2014
Dapagliflozin improves muscle insulin sensitivity but enhances endogenous glucose production.
    The Journal of clinical investigation, 2014, Volume: 124, Issue:2

    Topics: Benzhydryl Compounds; Blood Glucose; Body Weight; Diabetes Mellitus, Type 2; Fasting; Glucagon; Gluc

2014
Dapagliflozin improves muscle insulin sensitivity but enhances endogenous glucose production.
    The Journal of clinical investigation, 2014, Volume: 124, Issue:2

    Topics: Benzhydryl Compounds; Blood Glucose; Body Weight; Diabetes Mellitus, Type 2; Fasting; Glucagon; Gluc

2014
Dapagliflozin improves muscle insulin sensitivity but enhances endogenous glucose production.
    The Journal of clinical investigation, 2014, Volume: 124, Issue:2

    Topics: Benzhydryl Compounds; Blood Glucose; Body Weight; Diabetes Mellitus, Type 2; Fasting; Glucagon; Gluc

2014
Dapagliflozin improves muscle insulin sensitivity but enhances endogenous glucose production.
    The Journal of clinical investigation, 2014, Volume: 124, Issue:2

    Topics: Benzhydryl Compounds; Blood Glucose; Body Weight; Diabetes Mellitus, Type 2; Fasting; Glucagon; Gluc

2014
Dapagliflozin improves muscle insulin sensitivity but enhances endogenous glucose production.
    The Journal of clinical investigation, 2014, Volume: 124, Issue:2

    Topics: Benzhydryl Compounds; Blood Glucose; Body Weight; Diabetes Mellitus, Type 2; Fasting; Glucagon; Gluc

2014
Dapagliflozin improves muscle insulin sensitivity but enhances endogenous glucose production.
    The Journal of clinical investigation, 2014, Volume: 124, Issue:2

    Topics: Benzhydryl Compounds; Blood Glucose; Body Weight; Diabetes Mellitus, Type 2; Fasting; Glucagon; Gluc

2014
Dapagliflozin improves muscle insulin sensitivity but enhances endogenous glucose production.
    The Journal of clinical investigation, 2014, Volume: 124, Issue:2

    Topics: Benzhydryl Compounds; Blood Glucose; Body Weight; Diabetes Mellitus, Type 2; Fasting; Glucagon; Gluc

2014
Dapagliflozin improves muscle insulin sensitivity but enhances endogenous glucose production.
    The Journal of clinical investigation, 2014, Volume: 124, Issue:2

    Topics: Benzhydryl Compounds; Blood Glucose; Body Weight; Diabetes Mellitus, Type 2; Fasting; Glucagon; Gluc

2014
Dapagliflozin improves muscle insulin sensitivity but enhances endogenous glucose production.
    The Journal of clinical investigation, 2014, Volume: 124, Issue:2

    Topics: Benzhydryl Compounds; Blood Glucose; Body Weight; Diabetes Mellitus, Type 2; Fasting; Glucagon; Gluc

2014
Dapagliflozin improves muscle insulin sensitivity but enhances endogenous glucose production.
    The Journal of clinical investigation, 2014, Volume: 124, Issue:2

    Topics: Benzhydryl Compounds; Blood Glucose; Body Weight; Diabetes Mellitus, Type 2; Fasting; Glucagon; Gluc

2014
Dapagliflozin improves muscle insulin sensitivity but enhances endogenous glucose production.
    The Journal of clinical investigation, 2014, Volume: 124, Issue:2

    Topics: Benzhydryl Compounds; Blood Glucose; Body Weight; Diabetes Mellitus, Type 2; Fasting; Glucagon; Gluc

2014
Dapagliflozin improves muscle insulin sensitivity but enhances endogenous glucose production.
    The Journal of clinical investigation, 2014, Volume: 124, Issue:2

    Topics: Benzhydryl Compounds; Blood Glucose; Body Weight; Diabetes Mellitus, Type 2; Fasting; Glucagon; Gluc

2014
Dapagliflozin improves muscle insulin sensitivity but enhances endogenous glucose production.
    The Journal of clinical investigation, 2014, Volume: 124, Issue:2

    Topics: Benzhydryl Compounds; Blood Glucose; Body Weight; Diabetes Mellitus, Type 2; Fasting; Glucagon; Gluc

2014
Dapagliflozin improves muscle insulin sensitivity but enhances endogenous glucose production.
    The Journal of clinical investigation, 2014, Volume: 124, Issue:2

    Topics: Benzhydryl Compounds; Blood Glucose; Body Weight; Diabetes Mellitus, Type 2; Fasting; Glucagon; Gluc

2014
Dapagliflozin improves muscle insulin sensitivity but enhances endogenous glucose production.
    The Journal of clinical investigation, 2014, Volume: 124, Issue:2

    Topics: Benzhydryl Compounds; Blood Glucose; Body Weight; Diabetes Mellitus, Type 2; Fasting; Glucagon; Gluc

2014
Effects of short-term metformin therapy associated with levothyroxine dose decrement on TSH and thyroid hormone levels in patients with thyroid cancer.
    Minerva endocrinologica, 2014, Volume: 39, Issue:1

    Topics: Adenocarcinoma, Follicular; Adult; Body Weight; Carcinoma, Papillary; Dose-Response Relationship, Dr

2014
The effects of dipeptidyl peptidase-4 inhibitors in treatment of obese patients with type 2 diabetes.
    Medical archives (Sarajevo, Bosnia and Herzegovina), 2013, Volume: 67, Issue:5

    Topics: Adult; Aged; Blood Glucose; Blood Pressure; Body Mass Index; Body Weight; Cholesterol, LDL; Diabetes

2013
Empagliflozin as add-on to metformin in patients with type 2 diabetes: a 24-week, randomized, double-blind, placebo-controlled trial.
    Diabetes care, 2014, Volume: 37, Issue:6

    Topics: Benzhydryl Compounds; Blood Glucose; Blood Pressure; Body Weight; Cohort Studies; Diabetes Mellitus,

2014
Phosphodiesterase 4 inhibition as a potential new therapeutic target in obese women with polycystic ovary syndrome.
    The Journal of clinical endocrinology and metabolism, 2014, Volume: 99, Issue:8

    Topics: Adult; Aminopyridines; Benzamides; Body Weight; Cyclopropanes; Drug-Related Side Effects and Adverse

2014
Lifestyle and metformin interventions have a durable effect to lower CRP and tPA levels in the diabetes prevention program except in those who develop diabetes.
    Diabetes care, 2014, Volume: 37, Issue:8

    Topics: Adult; Aged; Aged, 80 and over; Body Weight; C-Reactive Protein; Diabetes Mellitus, Type 2; Female;

2014
Safety, efficacy and weight effect of two 11β-HSD1 inhibitors in metformin-treated patients with type 2 diabetes.
    Diabetes, obesity & metabolism, 2014, Volume: 16, Issue:11

    Topics: 11-beta-Hydroxysteroid Dehydrogenase Type 1; Adult; Aged; Austria; Blood Glucose; Body Weight; C-Pep

2014
Efficacy and safety comparison of add-on therapy with liraglutide, saxagliptin and vildagliptin, all in combination with current conventional oral hypoglycemic agents therapy in poorly controlled Chinese type 2 diabetes.
    Experimental and clinical endocrinology & diabetes : official journal, German Society of Endocrinology [and] German Diabetes Association, 2014, Volume: 122, Issue:8

    Topics: Adamantane; Adult; Asian People; Blood Glucose; Body Weight; China; Diabetes Mellitus, Type 2; Dipep

2014
Efficacy and safety of dulaglutide monotherapy versus metformin in type 2 diabetes in a randomized controlled trial (AWARD-3).
    Diabetes care, 2014, Volume: 37, Issue:8

    Topics: Adult; Aged; Blood Glucose; Body Weight; Diabetes Mellitus, Type 2; Double-Blind Method; Female; Glu

2014
Efficacy and safety of dulaglutide monotherapy versus metformin in type 2 diabetes in a randomized controlled trial (AWARD-3).
    Diabetes care, 2014, Volume: 37, Issue:8

    Topics: Adult; Aged; Blood Glucose; Body Weight; Diabetes Mellitus, Type 2; Double-Blind Method; Female; Glu

2014
Efficacy and safety of dulaglutide monotherapy versus metformin in type 2 diabetes in a randomized controlled trial (AWARD-3).
    Diabetes care, 2014, Volume: 37, Issue:8

    Topics: Adult; Aged; Blood Glucose; Body Weight; Diabetes Mellitus, Type 2; Double-Blind Method; Female; Glu

2014
Efficacy and safety of dulaglutide monotherapy versus metformin in type 2 diabetes in a randomized controlled trial (AWARD-3).
    Diabetes care, 2014, Volume: 37, Issue:8

    Topics: Adult; Aged; Blood Glucose; Body Weight; Diabetes Mellitus, Type 2; Double-Blind Method; Female; Glu

2014
HARMONY 3: 104-week randomized, double-blind, placebo- and active-controlled trial assessing the efficacy and safety of albiglutide compared with placebo, sitagliptin, and glimepiride in patients with type 2 diabetes taking metformin.
    Diabetes care, 2014, Volume: 37, Issue:8

    Topics: Aged; Body Weight; Diabetes Mellitus, Type 2; Double-Blind Method; Drug Therapy, Combination; Female

2014
Durability of glycaemic efficacy over 2 years with dapagliflozin versus glipizide as add-on therapies in patients whose type 2 diabetes mellitus is inadequately controlled with metformin.
    Diabetes, obesity & metabolism, 2014, Volume: 16, Issue:11

    Topics: Benzhydryl Compounds; Blood Glucose; Blood Pressure; Body Weight; Diabetes Mellitus, Type 2; Dose-Re

2014
Durability of glycaemic efficacy over 2 years with dapagliflozin versus glipizide as add-on therapies in patients whose type 2 diabetes mellitus is inadequately controlled with metformin.
    Diabetes, obesity & metabolism, 2014, Volume: 16, Issue:11

    Topics: Benzhydryl Compounds; Blood Glucose; Blood Pressure; Body Weight; Diabetes Mellitus, Type 2; Dose-Re

2014
Durability of glycaemic efficacy over 2 years with dapagliflozin versus glipizide as add-on therapies in patients whose type 2 diabetes mellitus is inadequately controlled with metformin.
    Diabetes, obesity & metabolism, 2014, Volume: 16, Issue:11

    Topics: Benzhydryl Compounds; Blood Glucose; Blood Pressure; Body Weight; Diabetes Mellitus, Type 2; Dose-Re

2014
Durability of glycaemic efficacy over 2 years with dapagliflozin versus glipizide as add-on therapies in patients whose type 2 diabetes mellitus is inadequately controlled with metformin.
    Diabetes, obesity & metabolism, 2014, Volume: 16, Issue:11

    Topics: Benzhydryl Compounds; Blood Glucose; Blood Pressure; Body Weight; Diabetes Mellitus, Type 2; Dose-Re

2014
Ipragliflozin in combination with metformin for the treatment of Japanese patients with type 2 diabetes: ILLUMINATE, a randomized, double-blind, placebo-controlled study.
    Diabetes, obesity & metabolism, 2015, Volume: 17, Issue:3

    Topics: Aged; Asian People; Blood Glucose; Body Weight; Diabetes Mellitus, Type 2; Double-Blind Method; Drug

2015
Effect of the sodium glucose co-transporter 2 inhibitor canagliflozin on plasma volume in patients with type 2 diabetes mellitus.
    Diabetes, obesity & metabolism, 2014, Volume: 16, Issue:11

    Topics: Adult; Aged; Antihypertensive Agents; Blood Glucose; Blood Pressure; Body Weight; Canagliflozin; Dia

2014
Glucagon-like peptide 1 receptor agonist or bolus insulin with optimized basal insulin in type 2 diabetes.
    Diabetes care, 2014, Volume: 37, Issue:10

    Topics: Aged; Blood Glucose; Body Weight; Diabetes Mellitus, Type 2; Drug Administration Schedule; Exenatide

2014
Glucagon-like peptide 1 receptor agonist or bolus insulin with optimized basal insulin in type 2 diabetes.
    Diabetes care, 2014, Volume: 37, Issue:10

    Topics: Aged; Blood Glucose; Body Weight; Diabetes Mellitus, Type 2; Drug Administration Schedule; Exenatide

2014
Glucagon-like peptide 1 receptor agonist or bolus insulin with optimized basal insulin in type 2 diabetes.
    Diabetes care, 2014, Volume: 37, Issue:10

    Topics: Aged; Blood Glucose; Body Weight; Diabetes Mellitus, Type 2; Drug Administration Schedule; Exenatide

2014
Glucagon-like peptide 1 receptor agonist or bolus insulin with optimized basal insulin in type 2 diabetes.
    Diabetes care, 2014, Volume: 37, Issue:10

    Topics: Aged; Blood Glucose; Body Weight; Diabetes Mellitus, Type 2; Drug Administration Schedule; Exenatide

2014
Glucagon-like peptide 1 receptor agonist or bolus insulin with optimized basal insulin in type 2 diabetes.
    Diabetes care, 2014, Volume: 37, Issue:10

    Topics: Aged; Blood Glucose; Body Weight; Diabetes Mellitus, Type 2; Drug Administration Schedule; Exenatide

2014
Glucagon-like peptide 1 receptor agonist or bolus insulin with optimized basal insulin in type 2 diabetes.
    Diabetes care, 2014, Volume: 37, Issue:10

    Topics: Aged; Blood Glucose; Body Weight; Diabetes Mellitus, Type 2; Drug Administration Schedule; Exenatide

2014
Glucagon-like peptide 1 receptor agonist or bolus insulin with optimized basal insulin in type 2 diabetes.
    Diabetes care, 2014, Volume: 37, Issue:10

    Topics: Aged; Blood Glucose; Body Weight; Diabetes Mellitus, Type 2; Drug Administration Schedule; Exenatide

2014
Glucagon-like peptide 1 receptor agonist or bolus insulin with optimized basal insulin in type 2 diabetes.
    Diabetes care, 2014, Volume: 37, Issue:10

    Topics: Aged; Blood Glucose; Body Weight; Diabetes Mellitus, Type 2; Drug Administration Schedule; Exenatide

2014
Glucagon-like peptide 1 receptor agonist or bolus insulin with optimized basal insulin in type 2 diabetes.
    Diabetes care, 2014, Volume: 37, Issue:10

    Topics: Aged; Blood Glucose; Body Weight; Diabetes Mellitus, Type 2; Drug Administration Schedule; Exenatide

2014
Twice-daily dapagliflozin co-administered with metformin in type 2 diabetes: a 16-week randomized, placebo-controlled clinical trial.
    Diabetes, obesity & metabolism, 2015, Volume: 17, Issue:1

    Topics: Aged; Benzhydryl Compounds; Body Weight; Diabetes Mellitus, Type 2; Dose-Response Relationship, Drug

2015
Canagliflozin provides durable glycemic improvements and body weight reduction over 104 weeks versus glimepiride in patients with type 2 diabetes on metformin: a randomized, double-blind, phase 3 study.
    Diabetes care, 2015, Volume: 38, Issue:3

    Topics: Blood Glucose; Body Weight; Canagliflozin; Diabetes Mellitus, Type 2; Double-Blind Method; Drug Ther

2015
Weight loss increases follicle stimulating hormone in overweight postmenopausal women [corrected].
    Obesity (Silver Spring, Md.), 2015, Volume: 23, Issue:1

    Topics: Aged; Behavior Therapy; Body Weight; Diabetes Mellitus, Type 2; Estradiol; Female; Follicle Stimulat

2015
[Efficacy of metformin in abdominal obesity].
    Terapevticheskii arkhiv, 2014, Volume: 86, Issue:8

    Topics: Adult; Blood Pressure; Body Mass Index; Body Weight; Female; Humans; Hypoglycemic Agents; Insulin Re

2014
Comparison of insulin glargine and liraglutide added to oral agents in patients with poorly controlled type 2 diabetes.
    Diabetes, obesity & metabolism, 2015, Volume: 17, Issue:2

    Topics: Administration, Oral; Aged; Blood Glucose; Body Mass Index; Body Weight; Diabetes Mellitus, Type 2;

2015
Efficacy and safety of dapagliflozin monotherapy in people with Type 2 diabetes: a randomized double-blind placebo-controlled 102-week trial.
    Diabetic medicine : a journal of the British Diabetic Association, 2015, Volume: 32, Issue:4

    Topics: Adolescent; Adult; Aged; Benzhydryl Compounds; Blood Glucose; Body Weight; Diabetes Mellitus, Type 2

2015
Saxagliptin efficacy and safety in patients with type 2 diabetes mellitus stratified by cardiovascular disease history and cardiovascular risk factors: analysis of 3 clinical trials.
    Postgraduate medicine, 2014, Volume: 126, Issue:6

    Topics: Adamantane; Adult; Blood Glucose; Body Weight; Cardiovascular Diseases; Diabetes Mellitus, Type 2; D

2014
Saxagliptin efficacy and safety in patients with type 2 diabetes mellitus stratified by cardiovascular disease history and cardiovascular risk factors: analysis of 3 clinical trials.
    Postgraduate medicine, 2014, Volume: 126, Issue:6

    Topics: Adamantane; Adult; Blood Glucose; Body Weight; Cardiovascular Diseases; Diabetes Mellitus, Type 2; D

2014
Saxagliptin efficacy and safety in patients with type 2 diabetes mellitus stratified by cardiovascular disease history and cardiovascular risk factors: analysis of 3 clinical trials.
    Postgraduate medicine, 2014, Volume: 126, Issue:6

    Topics: Adamantane; Adult; Blood Glucose; Body Weight; Cardiovascular Diseases; Diabetes Mellitus, Type 2; D

2014
Saxagliptin efficacy and safety in patients with type 2 diabetes mellitus stratified by cardiovascular disease history and cardiovascular risk factors: analysis of 3 clinical trials.
    Postgraduate medicine, 2014, Volume: 126, Issue:6

    Topics: Adamantane; Adult; Blood Glucose; Body Weight; Cardiovascular Diseases; Diabetes Mellitus, Type 2; D

2014
Saxagliptin efficacy and safety in patients with type 2 diabetes mellitus stratified by cardiovascular disease history and cardiovascular risk factors: analysis of 3 clinical trials.
    Postgraduate medicine, 2014, Volume: 126, Issue:6

    Topics: Adamantane; Adult; Blood Glucose; Body Weight; Cardiovascular Diseases; Diabetes Mellitus, Type 2; D

2014
Saxagliptin efficacy and safety in patients with type 2 diabetes mellitus stratified by cardiovascular disease history and cardiovascular risk factors: analysis of 3 clinical trials.
    Postgraduate medicine, 2014, Volume: 126, Issue:6

    Topics: Adamantane; Adult; Blood Glucose; Body Weight; Cardiovascular Diseases; Diabetes Mellitus, Type 2; D

2014
Saxagliptin efficacy and safety in patients with type 2 diabetes mellitus stratified by cardiovascular disease history and cardiovascular risk factors: analysis of 3 clinical trials.
    Postgraduate medicine, 2014, Volume: 126, Issue:6

    Topics: Adamantane; Adult; Blood Glucose; Body Weight; Cardiovascular Diseases; Diabetes Mellitus, Type 2; D

2014
Saxagliptin efficacy and safety in patients with type 2 diabetes mellitus stratified by cardiovascular disease history and cardiovascular risk factors: analysis of 3 clinical trials.
    Postgraduate medicine, 2014, Volume: 126, Issue:6

    Topics: Adamantane; Adult; Blood Glucose; Body Weight; Cardiovascular Diseases; Diabetes Mellitus, Type 2; D

2014
Saxagliptin efficacy and safety in patients with type 2 diabetes mellitus stratified by cardiovascular disease history and cardiovascular risk factors: analysis of 3 clinical trials.
    Postgraduate medicine, 2014, Volume: 126, Issue:6

    Topics: Adamantane; Adult; Blood Glucose; Body Weight; Cardiovascular Diseases; Diabetes Mellitus, Type 2; D

2014
Long-term efficacy and safety of canagliflozin over 104 weeks in patients aged 55-80 years with type 2 diabetes.
    Diabetes, obesity & metabolism, 2015, Volume: 17, Issue:3

    Topics: Aged; Aged, 80 and over; Blood Glucose; Blood Pressure; Body Weight; Canagliflozin; Cholesterol, HDL

2015
Dapagliflozin improves glycemic control and reduces body weight as add-on therapy to metformin plus sulfonylurea: a 24-week randomized, double-blind clinical trial.
    Diabetes care, 2015, Volume: 38, Issue:3

    Topics: Aged; Benzhydryl Compounds; Blood Glucose; Blood Pressure; Body Weight; Diabetes Mellitus, Type 2; D

2015
Dapagliflozin improves glycemic control and reduces body weight as add-on therapy to metformin plus sulfonylurea: a 24-week randomized, double-blind clinical trial.
    Diabetes care, 2015, Volume: 38, Issue:3

    Topics: Aged; Benzhydryl Compounds; Blood Glucose; Blood Pressure; Body Weight; Diabetes Mellitus, Type 2; D

2015
Dapagliflozin improves glycemic control and reduces body weight as add-on therapy to metformin plus sulfonylurea: a 24-week randomized, double-blind clinical trial.
    Diabetes care, 2015, Volume: 38, Issue:3

    Topics: Aged; Benzhydryl Compounds; Blood Glucose; Blood Pressure; Body Weight; Diabetes Mellitus, Type 2; D

2015
Dapagliflozin improves glycemic control and reduces body weight as add-on therapy to metformin plus sulfonylurea: a 24-week randomized, double-blind clinical trial.
    Diabetes care, 2015, Volume: 38, Issue:3

    Topics: Aged; Benzhydryl Compounds; Blood Glucose; Blood Pressure; Body Weight; Diabetes Mellitus, Type 2; D

2015
Long-term glycaemic response and tolerability of dapagliflozin versus a sulphonylurea as add-on therapy to metformin in patients with type 2 diabetes: 4-year data.
    Diabetes, obesity & metabolism, 2015, Volume: 17, Issue:6

    Topics: Aged; Benzhydryl Compounds; Blood Glucose; Blood Pressure; Body Weight; Diabetes Mellitus, Type 2; D

2015
Dose-ranging efficacy and safety study of ertugliflozin, a sodium-glucose co-transporter 2 inhibitor, in patients with type 2 diabetes on a background of metformin.
    Diabetes, obesity & metabolism, 2015, Volume: 17, Issue:6

    Topics: Adult; Aged; Blood Glucose; Blood Pressure; Body Weight; Bridged Bicyclo Compounds, Heterocyclic; Di

2015
Design of FLAT-SUGAR: Randomized Trial of Prandial Insulin Versus Prandial GLP-1 Receptor Agonist Together With Basal Insulin and Metformin for High-Risk Type 2 Diabetes.
    Diabetes care, 2015, Volume: 38, Issue:8

    Topics: Albuminuria; Biomarkers; Blood Glucose; Body Weight; Diabetes Mellitus, Type 2; Diabetic Angiopathie

2015
The Efficacy and Safety of Chinese Herbal Medicine Jinlida as Add-On Medication in Type 2 Diabetes Patients Ineffectively Managed by Metformin Monotherapy: A Double-Blind, Randomized, Placebo-Controlled, Multicenter Trial.
    PloS one, 2015, Volume: 10, Issue:6

    Topics: Body Weight; Diabetes Mellitus, Type 2; Double-Blind Method; Drug Therapy, Combination; Drugs, Chine

2015
Empagliflozin as Add-on Therapy to Pioglitazone With or Without Metformin in Patients With Type 2 Diabetes Mellitus.
    Clinical therapeutics, 2015, Volume: 37, Issue:8

    Topics: Adult; Aged; Benzhydryl Compounds; Blood Glucose; Blood Pressure; Body Weight; Diabetes Mellitus, Ty

2015
Empagliflozin as Add-on Therapy to Pioglitazone With or Without Metformin in Patients With Type 2 Diabetes Mellitus.
    Clinical therapeutics, 2015, Volume: 37, Issue:8

    Topics: Adult; Aged; Benzhydryl Compounds; Blood Glucose; Blood Pressure; Body Weight; Diabetes Mellitus, Ty

2015
Empagliflozin as Add-on Therapy to Pioglitazone With or Without Metformin in Patients With Type 2 Diabetes Mellitus.
    Clinical therapeutics, 2015, Volume: 37, Issue:8

    Topics: Adult; Aged; Benzhydryl Compounds; Blood Glucose; Blood Pressure; Body Weight; Diabetes Mellitus, Ty

2015
Empagliflozin as Add-on Therapy to Pioglitazone With or Without Metformin in Patients With Type 2 Diabetes Mellitus.
    Clinical therapeutics, 2015, Volume: 37, Issue:8

    Topics: Adult; Aged; Benzhydryl Compounds; Blood Glucose; Blood Pressure; Body Weight; Diabetes Mellitus, Ty

2015
A novel and selective sodium-glucose cotransporter-2 inhibitor, tofogliflozin, improves glycaemic control and lowers body weight in patients with type 2 diabetes mellitus.
    Diabetes, obesity & metabolism, 2015, Volume: 17, Issue:10

    Topics: Adult; Aged; Benzhydryl Compounds; Blood Glucose; Blood Pressure; Body Weight; Combined Modality The

2015
Efficacy and safety of liraglutide versus placebo added to basal insulin analogues (with or without metformin) in patients with type 2 diabetes: a randomized, placebo-controlled trial.
    Diabetes, obesity & metabolism, 2015, Volume: 17, Issue:11

    Topics: Aged; Blood Glucose; Blood Pressure; Body Weight; Diabetes Mellitus, Type 2; Double-Blind Method; Dr

2015
Durability and tolerability of dapagliflozin over 52 weeks as add-on to metformin and sulphonylurea in type 2 diabetes.
    Diabetes, obesity & metabolism, 2015, Volume: 17, Issue:11

    Topics: Aged; Benzhydryl Compounds; Blood Glucose; Blood Pressure; Body Weight; Cholesterol; Diabetes Mellit

2015
Empagliflozin as add-on to metformin plus sulphonylurea in patients with type 2 diabetes.
    Diabetes research and clinical practice, 2015, Volume: 110, Issue:1

    Topics: Adult; Aged; Benzhydryl Compounds; Blood Glucose; Blood Pressure; Body Weight; Diabetes Mellitus, Ty

2015
Effects of Liraglutide Monotherapy on Beta Cell Function and Pancreatic Enzymes Compared with Metformin in Japanese Overweight/Obese Patients with Type 2 Diabetes Mellitus: A Subpopulation Analysis of the KIND-LM Randomized Trial.
    Clinical drug investigation, 2015, Volume: 35, Issue:10

    Topics: Amylases; Blood Glucose; Body Fat Distribution; Body Weight; Diabetes Mellitus, Type 2; Drug Adminis

2015
The effects of metformin treatment of gestational diabetes on maternal weight and glucose tolerance postpartum--a prospective follow-up study.
    Acta obstetricia et gynecologica Scandinavica, 2016, Volume: 95, Issue:1

    Topics: Adult; Blood Glucose; Body Weight; Diabetes, Gestational; Female; Follow-Up Studies; Glucose Toleran

2016
Efficacy and safety of canagliflozin in patients with type 2 diabetes mellitus from Latin America.
    Current medical research and opinion, 2016, Volume: 32, Issue:3

    Topics: Adult; Aged; Blood Glucose; Blood Pressure; Body Weight; Canagliflozin; Diabetes Mellitus, Type 2; D

2016
Efficacy and safety of canagliflozin in patients with type 2 diabetes mellitus from Latin America.
    Current medical research and opinion, 2016, Volume: 32, Issue:3

    Topics: Adult; Aged; Blood Glucose; Blood Pressure; Body Weight; Canagliflozin; Diabetes Mellitus, Type 2; D

2016
Efficacy and safety of canagliflozin in patients with type 2 diabetes mellitus from Latin America.
    Current medical research and opinion, 2016, Volume: 32, Issue:3

    Topics: Adult; Aged; Blood Glucose; Blood Pressure; Body Weight; Canagliflozin; Diabetes Mellitus, Type 2; D

2016
Efficacy and safety of canagliflozin in patients with type 2 diabetes mellitus from Latin America.
    Current medical research and opinion, 2016, Volume: 32, Issue:3

    Topics: Adult; Aged; Blood Glucose; Blood Pressure; Body Weight; Canagliflozin; Diabetes Mellitus, Type 2; D

2016
Efficacy and safety of canagliflozin in patients with type 2 diabetes mellitus from Latin America.
    Current medical research and opinion, 2016, Volume: 32, Issue:3

    Topics: Adult; Aged; Blood Glucose; Blood Pressure; Body Weight; Canagliflozin; Diabetes Mellitus, Type 2; D

2016
Efficacy and safety of canagliflozin in patients with type 2 diabetes mellitus from Latin America.
    Current medical research and opinion, 2016, Volume: 32, Issue:3

    Topics: Adult; Aged; Blood Glucose; Blood Pressure; Body Weight; Canagliflozin; Diabetes Mellitus, Type 2; D

2016
Efficacy and safety of canagliflozin in patients with type 2 diabetes mellitus from Latin America.
    Current medical research and opinion, 2016, Volume: 32, Issue:3

    Topics: Adult; Aged; Blood Glucose; Blood Pressure; Body Weight; Canagliflozin; Diabetes Mellitus, Type 2; D

2016
Efficacy and safety of canagliflozin in patients with type 2 diabetes mellitus from Latin America.
    Current medical research and opinion, 2016, Volume: 32, Issue:3

    Topics: Adult; Aged; Blood Glucose; Blood Pressure; Body Weight; Canagliflozin; Diabetes Mellitus, Type 2; D

2016
Efficacy and safety of canagliflozin in patients with type 2 diabetes mellitus from Latin America.
    Current medical research and opinion, 2016, Volume: 32, Issue:3

    Topics: Adult; Aged; Blood Glucose; Blood Pressure; Body Weight; Canagliflozin; Diabetes Mellitus, Type 2; D

2016
Efficacy and safety of canagliflozin in patients with type 2 diabetes mellitus from Latin America.
    Current medical research and opinion, 2016, Volume: 32, Issue:3

    Topics: Adult; Aged; Blood Glucose; Blood Pressure; Body Weight; Canagliflozin; Diabetes Mellitus, Type 2; D

2016
Efficacy and safety of canagliflozin in patients with type 2 diabetes mellitus from Latin America.
    Current medical research and opinion, 2016, Volume: 32, Issue:3

    Topics: Adult; Aged; Blood Glucose; Blood Pressure; Body Weight; Canagliflozin; Diabetes Mellitus, Type 2; D

2016
Efficacy and safety of canagliflozin in patients with type 2 diabetes mellitus from Latin America.
    Current medical research and opinion, 2016, Volume: 32, Issue:3

    Topics: Adult; Aged; Blood Glucose; Blood Pressure; Body Weight; Canagliflozin; Diabetes Mellitus, Type 2; D

2016
Efficacy and safety of canagliflozin in patients with type 2 diabetes mellitus from Latin America.
    Current medical research and opinion, 2016, Volume: 32, Issue:3

    Topics: Adult; Aged; Blood Glucose; Blood Pressure; Body Weight; Canagliflozin; Diabetes Mellitus, Type 2; D

2016
Efficacy and safety of canagliflozin in patients with type 2 diabetes mellitus from Latin America.
    Current medical research and opinion, 2016, Volume: 32, Issue:3

    Topics: Adult; Aged; Blood Glucose; Blood Pressure; Body Weight; Canagliflozin; Diabetes Mellitus, Type 2; D

2016
Efficacy and safety of canagliflozin in patients with type 2 diabetes mellitus from Latin America.
    Current medical research and opinion, 2016, Volume: 32, Issue:3

    Topics: Adult; Aged; Blood Glucose; Blood Pressure; Body Weight; Canagliflozin; Diabetes Mellitus, Type 2; D

2016
Efficacy and safety of canagliflozin in patients with type 2 diabetes mellitus from Latin America.
    Current medical research and opinion, 2016, Volume: 32, Issue:3

    Topics: Adult; Aged; Blood Glucose; Blood Pressure; Body Weight; Canagliflozin; Diabetes Mellitus, Type 2; D

2016
Efficacy and safety of canagliflozin in patients with type 2 diabetes mellitus from Latin America.
    Current medical research and opinion, 2016, Volume: 32, Issue:3

    Topics: Adult; Aged; Blood Glucose; Blood Pressure; Body Weight; Canagliflozin; Diabetes Mellitus, Type 2; D

2016
Efficacy and safety of canagliflozin in patients with type 2 diabetes mellitus from Latin America.
    Current medical research and opinion, 2016, Volume: 32, Issue:3

    Topics: Adult; Aged; Blood Glucose; Blood Pressure; Body Weight; Canagliflozin; Diabetes Mellitus, Type 2; D

2016
Efficacy and safety of canagliflozin in patients with type 2 diabetes mellitus from Latin America.
    Current medical research and opinion, 2016, Volume: 32, Issue:3

    Topics: Adult; Aged; Blood Glucose; Blood Pressure; Body Weight; Canagliflozin; Diabetes Mellitus, Type 2; D

2016
Efficacy and safety of canagliflozin in patients with type 2 diabetes mellitus from Latin America.
    Current medical research and opinion, 2016, Volume: 32, Issue:3

    Topics: Adult; Aged; Blood Glucose; Blood Pressure; Body Weight; Canagliflozin; Diabetes Mellitus, Type 2; D

2016
Efficacy and safety of canagliflozin in patients with type 2 diabetes mellitus from Latin America.
    Current medical research and opinion, 2016, Volume: 32, Issue:3

    Topics: Adult; Aged; Blood Glucose; Blood Pressure; Body Weight; Canagliflozin; Diabetes Mellitus, Type 2; D

2016
Efficacy and safety of canagliflozin in patients with type 2 diabetes mellitus from Latin America.
    Current medical research and opinion, 2016, Volume: 32, Issue:3

    Topics: Adult; Aged; Blood Glucose; Blood Pressure; Body Weight; Canagliflozin; Diabetes Mellitus, Type 2; D

2016
Efficacy and safety of canagliflozin in patients with type 2 diabetes mellitus from Latin America.
    Current medical research and opinion, 2016, Volume: 32, Issue:3

    Topics: Adult; Aged; Blood Glucose; Blood Pressure; Body Weight; Canagliflozin; Diabetes Mellitus, Type 2; D

2016
Efficacy and safety of canagliflozin in patients with type 2 diabetes mellitus from Latin America.
    Current medical research and opinion, 2016, Volume: 32, Issue:3

    Topics: Adult; Aged; Blood Glucose; Blood Pressure; Body Weight; Canagliflozin; Diabetes Mellitus, Type 2; D

2016
Efficacy and safety of canagliflozin in patients with type 2 diabetes mellitus from Latin America.
    Current medical research and opinion, 2016, Volume: 32, Issue:3

    Topics: Adult; Aged; Blood Glucose; Blood Pressure; Body Weight; Canagliflozin; Diabetes Mellitus, Type 2; D

2016
Efficacy and safety of dapagliflozin in Asian patients with type 2 diabetes after metformin failure: A randomized controlled trial.
    Journal of diabetes, 2016, Volume: 8, Issue:6

    Topics: Adult; Benzhydryl Compounds; Blood Glucose; Blood Pressure; Body Weight; Diabetes Mellitus, Type 2;

2016
Effect of Metformin Added to Insulin on Glycemic Control Among Overweight/Obese Adolescents With Type 1 Diabetes: A Randomized Clinical Trial.
    JAMA, 2015, Dec-01, Volume: 314, Issue:21

    Topics: Adolescent; Blood Glucose; Body Mass Index; Body Weight; Child; Diabetes Mellitus, Type 1; Double-Bl

2015
Metformin treatment of antipsychotic-induced dyslipidemia: an analysis of two randomized, placebo-controlled trials.
    Molecular psychiatry, 2016, Volume: 21, Issue:11

    Topics: Adult; Antipsychotic Agents; Blood Glucose; Body Weight; Double-Blind Method; Dyslipidemias; Female;

2016
Metformin versus placebo in combination with insulin analogues in patients with type 2 diabetes mellitus-the randomised, blinded Copenhagen Insulin and Metformin Therapy (CIMT) trial.
    BMJ open, 2016, Feb-25, Volume: 6, Issue:2

    Topics: Blood Glucose; Body Weight; Carotid Intima-Media Thickness; Denmark; Diabetes Mellitus, Type 2; Glyc

2016
Effects of biphasic, basal-bolus or basal insulin analogue treatments on carotid intima-media thickness in patients with type 2 diabetes mellitus: the randomised Copenhagen Insulin and Metformin Therapy (CIMT) trial.
    BMJ open, 2016, Feb-25, Volume: 6, Issue:2

    Topics: Blood Glucose; Body Weight; Carotid Intima-Media Thickness; Denmark; Diabetes Mellitus, Type 2; Drug

2016
Efficacy and safety of liraglutide versus sitagliptin, both in combination with metformin, in Chinese patients with type 2 diabetes: a 26-week, open-label, randomized, active comparator clinical trial.
    Diabetes, obesity & metabolism, 2016, Volume: 18, Issue:8

    Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anorexia; Asian People; Blood Glucose; Body Weight; Chin

2016
Safety, tolerability, pharmacokinetics and pharmacodynamics of AZP-531, a first-in-class analogue of unacylated ghrelin, in healthy and overweight/obese subjects and subjects with type 2 diabetes.
    Diabetes, obesity & metabolism, 2016, Volume: 18, Issue:9

    Topics: Adolescent; Adult; Aged; Blood Glucose; Body Weight; Diabetes Mellitus, Type 2; Diarrhea; Double-Bli

2016
Weight and Glucose Reduction Observed with a Combination of Nutritional Agents in Rodent Models Does Not Translate to Humans in a Randomized Clinical Trial with Healthy Volunteers and Subjects with Type 2 Diabetes.
    PloS one, 2016, Volume: 11, Issue:4

    Topics: Adolescent; Adult; Aged; Animals; Biological Factors; Blood Glucose; Body Weight; Diabetes Mellitus,

2016
Comparative evaluation of the therapeutic effect of metformin monotherapy with metformin and acupuncture combined therapy on weight loss and insulin sensitivity in diabetic patients.
    Nutrition & diabetes, 2016, May-02, Volume: 6

    Topics: Acupuncture Therapy; Adiponectin; Adult; Biomarkers; Body Mass Index; Body Weight; Cholesterol, HDL;

2016
Efficacy and safety of titrated canagliflozin in patients with type 2 diabetes mellitus inadequately controlled on metformin and sitagliptin.
    Diabetes, obesity & metabolism, 2016, Volume: 18, Issue:8

    Topics: Aged; Blood Glucose; Blood Pressure; Body Weight; Canagliflozin; Diabetes Mellitus, Type 2; Double-B

2016
Weight change in the management of youth-onset type 2 diabetes: the TODAY clinical trial experience.
    Pediatric obesity, 2017, Volume: 12, Issue:4

    Topics: Adolescent; Anthropometry; Blood Glucose; Body Weight; Child; Diabetes Mellitus, Type 2; Drug Combin

2017
Glucose Variability in a 26-Week Randomized Comparison of Mealtime Treatment With Rapid-Acting Insulin Versus GLP-1 Agonist in Participants With Type 2 Diabetes at High Cardiovascular Risk.
    Diabetes care, 2016, Volume: 39, Issue:6

    Topics: Adult; Aged; Alanine Transaminase; Arrhythmias, Cardiac; Blood Glucose; Body Weight; Cardiovascular

2016
Glucose Variability in a 26-Week Randomized Comparison of Mealtime Treatment With Rapid-Acting Insulin Versus GLP-1 Agonist in Participants With Type 2 Diabetes at High Cardiovascular Risk.
    Diabetes care, 2016, Volume: 39, Issue:6

    Topics: Adult; Aged; Alanine Transaminase; Arrhythmias, Cardiac; Blood Glucose; Body Weight; Cardiovascular

2016
Glucose Variability in a 26-Week Randomized Comparison of Mealtime Treatment With Rapid-Acting Insulin Versus GLP-1 Agonist in Participants With Type 2 Diabetes at High Cardiovascular Risk.
    Diabetes care, 2016, Volume: 39, Issue:6

    Topics: Adult; Aged; Alanine Transaminase; Arrhythmias, Cardiac; Blood Glucose; Body Weight; Cardiovascular

2016
Glucose Variability in a 26-Week Randomized Comparison of Mealtime Treatment With Rapid-Acting Insulin Versus GLP-1 Agonist in Participants With Type 2 Diabetes at High Cardiovascular Risk.
    Diabetes care, 2016, Volume: 39, Issue:6

    Topics: Adult; Aged; Alanine Transaminase; Arrhythmias, Cardiac; Blood Glucose; Body Weight; Cardiovascular

2016
Prandial Options to Advance Basal Insulin Glargine Therapy: Testing Lixisenatide Plus Basal Insulin Versus Insulin Glulisine Either as Basal-Plus or Basal-Bolus in Type 2 Diabetes: The GetGoal Duo-2 Trial.
    Diabetes care, 2016, Volume: 39, Issue:8

    Topics: Aged; Blood Glucose; Body Mass Index; Body Weight; Diabetes Mellitus, Type 2; Drug Therapy, Combinat

2016
Efficacy and safety of sitagliptin/metformin fixed-dose combination compared with glimepiride in patients with type 2 diabetes: A multicenter randomized double-blind study.
    Journal of diabetes, 2017, Volume: 9, Issue:4

    Topics: Adult; Blood Glucose; Body Weight; Diabetes Mellitus, Type 2; Diarrhea; Double-Blind Method; Drug Th

2017
Efficacy and Safety of LixiLan, a Titratable Fixed-Ratio Combination of Lixisenatide and Insulin Glargine, Versus Insulin Glargine in Type 2 Diabetes Inadequately Controlled on Metformin Monotherapy: The LixiLan Proof-of-Concept Randomized Trial.
    Diabetes care, 2016, Volume: 39, Issue:9

    Topics: Aged; Blood Glucose; Body Weight; Diabetes Mellitus, Type 2; Drug Combinations; Drug Therapy, Combin

2016
Once-Daily Liraglutide Versus Lixisenatide as Add-on to Metformin in Type 2 Diabetes: A 26-Week Randomized Controlled Clinical Trial.
    Diabetes care, 2016, Volume: 39, Issue:9

    Topics: Adult; Aged; Aged, 80 and over; Blood Glucose; Body Weight; Diabetes Mellitus, Type 2; Drug Administ

2016
Efficacy and safety of switching from sitagliptin to liraglutide in subjects with type 2 diabetes (LIRA-SWITCH): a randomized, double-blind, double-dummy, active-controlled 26-week trial.
    Diabetes, obesity & metabolism, 2016, Volume: 18, Issue:12

    Topics: Adult; Aged; Aged, 80 and over; Asia; Blood Glucose; Body Weight; Diabetes Mellitus, Type 2; Double-

2016
Efficacy and safety of triple therapy with dapagliflozin add-on to saxagliptin plus metformin over 52 weeks in patients with type 2 diabetes.
    Diabetes, obesity & metabolism, 2016, Volume: 18, Issue:11

    Topics: Adamantane; Adult; Benzhydryl Compounds; Blood Glucose; Body Weight; Diabetes Mellitus, Type 2; Dipe

2016
Canagliflozin provides greater attainment of both HbA1c and body weight reduction versus sitagliptin in patients with type 2 diabetes.
    Postgraduate medicine, 2016, Volume: 128, Issue:8

    Topics: Adult; Aged; Aged, 80 and over; Body Mass Index; Body Weight; Canagliflozin; Diabetes Mellitus, Type

2016
Canagliflozin provides greater attainment of both HbA1c and body weight reduction versus sitagliptin in patients with type 2 diabetes.
    Postgraduate medicine, 2016, Volume: 128, Issue:8

    Topics: Adult; Aged; Aged, 80 and over; Body Mass Index; Body Weight; Canagliflozin; Diabetes Mellitus, Type

2016
Canagliflozin provides greater attainment of both HbA1c and body weight reduction versus sitagliptin in patients with type 2 diabetes.
    Postgraduate medicine, 2016, Volume: 128, Issue:8

    Topics: Adult; Aged; Aged, 80 and over; Body Mass Index; Body Weight; Canagliflozin; Diabetes Mellitus, Type

2016
Canagliflozin provides greater attainment of both HbA1c and body weight reduction versus sitagliptin in patients with type 2 diabetes.
    Postgraduate medicine, 2016, Volume: 128, Issue:8

    Topics: Adult; Aged; Aged, 80 and over; Body Mass Index; Body Weight; Canagliflozin; Diabetes Mellitus, Type

2016
One-year efficacy and safety of saxagliptin add-on in patients receiving dapagliflozin and metformin.
    Diabetes, obesity & metabolism, 2016, Volume: 18, Issue:11

    Topics: Adamantane; Adult; Aged; Benzhydryl Compounds; Blood Glucose; Body Weight; Diabetes Mellitus, Type 2

2016
Effects of SLC22A1 Polymorphisms on Metformin-Induced Reductions in Adiposity and Metformin Pharmacokinetics in Obese Children With Insulin Resistance.
    Journal of clinical pharmacology, 2017, Volume: 57, Issue:2

    Topics: Adiposity; Body Weight; Child; Double-Blind Method; Female; Genotype; Glomerular Filtration Rate; Hu

2017
Phase II study of metformin for reduction of obesity-associated breast cancer risk: a randomized controlled trial protocol.
    BMC cancer, 2016, 07-19, Volume: 16

    Topics: Adiponectin; Adult; Body Weight; Breast; Breast Neoplasms; Double-Blind Method; Humans; Hypoglycemic

2016
Pharmacodynamic Effects of Single and Multiple Doses of Empagliflozin in Patients With Type 2 Diabetes.
    Clinical therapeutics, 2016, Volume: 38, Issue:10

    Topics: Adult; Aged; Benzhydryl Compounds; Blood Glucose; Body Weight; Cross-Over Studies; Diabetes Mellitus

2016
The effects of exenatide twice daily compared to insulin lispro added to basal insulin in Latin American patients with type 2 diabetes: A retrospective analysis of the 4B trial.
    Diabetes research and clinical practice, 2016, Volume: 122

    Topics: Adult; Aged; Argentina; Blood Glucose; Body Weight; Diabetes Mellitus, Type 2; Drug Administration S

2016
Sustained influence of metformin therapy on circulating glucagon-like peptide-1 levels in individuals with and without type 2 diabetes.
    Diabetes, obesity & metabolism, 2017, Volume: 19, Issue:3

    Topics: Adult; Aged; Blood Glucose; Body Weight; Case-Control Studies; Diabetes Mellitus, Type 2; Double-Bli

2017
Metformin in adults with type 1 diabetes: Design and methods of REducing with MetfOrmin Vascular Adverse Lesions (REMOVAL): An international multicentre trial.
    Diabetes, obesity & metabolism, 2017, Volume: 19, Issue:4

    Topics: Adult; Atherosclerosis; Blood Glucose; Body Weight; Carotid Intima-Media Thickness; Cholesterol, LDL

2017
Effects of Low Dose Metformin on Metabolic Traits in Clozapine-Treated Schizophrenia Patients: An Exploratory Twelve-Week Randomized, Double-Blind, Placebo-Controlled Study.
    PloS one, 2016, Volume: 11, Issue:12

    Topics: Adult; Antipsychotic Agents; Body Mass Index; Body Weight; Clozapine; Double-Blind Method; Female; H

2016
Effects of Low Dose Metformin on Metabolic Traits in Clozapine-Treated Schizophrenia Patients: An Exploratory Twelve-Week Randomized, Double-Blind, Placebo-Controlled Study.
    PloS one, 2016, Volume: 11, Issue:12

    Topics: Adult; Antipsychotic Agents; Body Mass Index; Body Weight; Clozapine; Double-Blind Method; Female; H

2016
Effects of Low Dose Metformin on Metabolic Traits in Clozapine-Treated Schizophrenia Patients: An Exploratory Twelve-Week Randomized, Double-Blind, Placebo-Controlled Study.
    PloS one, 2016, Volume: 11, Issue:12

    Topics: Adult; Antipsychotic Agents; Body Mass Index; Body Weight; Clozapine; Double-Blind Method; Female; H

2016
Effects of Low Dose Metformin on Metabolic Traits in Clozapine-Treated Schizophrenia Patients: An Exploratory Twelve-Week Randomized, Double-Blind, Placebo-Controlled Study.
    PloS one, 2016, Volume: 11, Issue:12

    Topics: Adult; Antipsychotic Agents; Body Mass Index; Body Weight; Clozapine; Double-Blind Method; Female; H

2016
Short-term effectiveness of low dose liraglutide in combination with metformin versus high dose liraglutide alone in treatment of obese PCOS: randomized trial.
    BMC endocrine disorders, 2017, Jan-31, Volume: 17, Issue:1

    Topics: Adult; Biomarkers; Blood Glucose; Body Weight; Drug Therapy, Combination; Female; Follow-Up Studies;

2017
Short-term effectiveness of low dose liraglutide in combination with metformin versus high dose liraglutide alone in treatment of obese PCOS: randomized trial.
    BMC endocrine disorders, 2017, Jan-31, Volume: 17, Issue:1

    Topics: Adult; Biomarkers; Blood Glucose; Body Weight; Drug Therapy, Combination; Female; Follow-Up Studies;

2017
Short-term effectiveness of low dose liraglutide in combination with metformin versus high dose liraglutide alone in treatment of obese PCOS: randomized trial.
    BMC endocrine disorders, 2017, Jan-31, Volume: 17, Issue:1

    Topics: Adult; Biomarkers; Blood Glucose; Body Weight; Drug Therapy, Combination; Female; Follow-Up Studies;

2017
Short-term effectiveness of low dose liraglutide in combination with metformin versus high dose liraglutide alone in treatment of obese PCOS: randomized trial.
    BMC endocrine disorders, 2017, Jan-31, Volume: 17, Issue:1

    Topics: Adult; Biomarkers; Blood Glucose; Body Weight; Drug Therapy, Combination; Female; Follow-Up Studies;

2017
Use of metformin in obese adolescents with hyperinsulinemia: a 6-month, randomized, double-blind, placebo-controlled clinical trial.
    Journal of pediatric endocrinology & metabolism : JPEM, 2008, Volume: 21, Issue:4

    Topics: Adolescent; Body Weight; Child; Double-Blind Method; Female; Humans; Hyperinsulinism; Hypoglycemic A

2008
Metformin improves endothelial function in normoinsulinemic PCOS patients: a new prospective.
    Human reproduction (Oxford, England), 2008, Volume: 23, Issue:9

    Topics: Adult; Androgens; Body Weight; Brachial Artery; Endothelium, Vascular; Female; Humans; Insulin; Metf

2008
Treatment of non-alcoholic fatty liver disease with metformin versus lifestyle intervention in insulin-resistant adolescents.
    Pediatric diabetes, 2009, Volume: 10, Issue:1

    Topics: Adolescent; Alanine Transaminase; Aspartate Aminotransferases; Body Mass Index; Body Weight; Child;

2009
Treatment of non-alcoholic fatty liver disease with metformin versus lifestyle intervention in insulin-resistant adolescents.
    Pediatric diabetes, 2009, Volume: 10, Issue:1

    Topics: Adolescent; Alanine Transaminase; Aspartate Aminotransferases; Body Mass Index; Body Weight; Child;

2009
Treatment of non-alcoholic fatty liver disease with metformin versus lifestyle intervention in insulin-resistant adolescents.
    Pediatric diabetes, 2009, Volume: 10, Issue:1

    Topics: Adolescent; Alanine Transaminase; Aspartate Aminotransferases; Body Mass Index; Body Weight; Child;

2009
Treatment of non-alcoholic fatty liver disease with metformin versus lifestyle intervention in insulin-resistant adolescents.
    Pediatric diabetes, 2009, Volume: 10, Issue:1

    Topics: Adolescent; Alanine Transaminase; Aspartate Aminotransferases; Body Mass Index; Body Weight; Child;

2009
Effect of adjunct metformin treatment in patients with type-1 diabetes and persistent inadequate glycaemic control. A randomized study.
    PloS one, 2008, Volume: 3, Issue:10

    Topics: Adult; Blood Glucose; Body Weight; Diabetes Mellitus, Type 1; Female; Glycated Hemoglobin; Humans; H

2008
Antiandrogenic contraceptives increase serum adiponectin in obese polycystic ovary syndrome patients.
    Obesity (Silver Spring, Md.), 2009, Volume: 17, Issue:1

    Topics: Adipocytes; Adiponectin; Adipose Tissue; Adult; Androgen Antagonists; Area Under Curve; Body Weight;

2009
Fifty-two-week efficacy and safety of vildagliptin vs. glimepiride in patients with type 2 diabetes mellitus inadequately controlled on metformin monotherapy.
    Diabetes, obesity & metabolism, 2009, Volume: 11, Issue:2

    Topics: Adamantane; Blood Glucose; Body Weight; Diabetes Mellitus, Type 2; Double-Blind Method; Drug Adminis

2009
Comparison of vildagliptin and metformin monotherapy in elderly patients with type 2 diabetes: a 24-week, double-blind, randomized trial.
    Diabetes, obesity & metabolism, 2009, Volume: 11, Issue:8

    Topics: Adamantane; Aged; Aged, 80 and over; Blood Glucose; Body Weight; Diabetes Mellitus, Type 2; Dipeptid

2009
Rosiglitazone evaluated for cardiovascular outcomes in oral agent combination therapy for type 2 diabetes (RECORD): a multicentre, randomised, open-label trial.
    Lancet (London, England), 2009, Jun-20, Volume: 373, Issue:9681

    Topics: Administration, Oral; Angina, Unstable; Body Weight; Cholesterol, HDL; Cholesterol, LDL; Diabetes Me

2009
Comparison of vildagliptin and pioglitazone in patients with type 2 diabetes inadequately controlled with metformin.
    Diabetes, obesity & metabolism, 2009, Volume: 11, Issue:6

    Topics: Adamantane; Adolescent; Adult; Aged; Blood Glucose; Body Weight; Diabetes Mellitus, Type 2; Dipeptid

2009
Extended release metformin for metabolic control assistance during prolonged clozapine administration: a 14 week, double-blind, parallel group, placebo-controlled study.
    Schizophrenia research, 2009, Volume: 113, Issue:1

    Topics: Adult; Anthropometry; Antipsychotic Agents; Blood Glucose; Blood Pressure; Body Mass Index; Body Wei

2009
Effects of bed-time insulin versus pioglitazone on abdominal fat accumulation, inflammation and gene expression in adipose tissue in patients with type 2 diabetes.
    Diabetes research and clinical practice, 2009, Volume: 86, Issue:1

    Topics: Adipose Tissue; Adolescent; Adult; Aged; Aged, 80 and over; Antigens, CD; Antigens, Differentiation,

2009
Liraglutide vs insulin glargine and placebo in combination with metformin and sulfonylurea therapy in type 2 diabetes mellitus (LEAD-5 met+SU): a randomised controlled trial.
    Diabetologia, 2009, Volume: 52, Issue:10

    Topics: Adolescent; Adult; Aged; Aged, 80 and over; Blood Glucose; Body Weight; Diabetes Mellitus, Type 2; D

2009
Liraglutide vs insulin glargine and placebo in combination with metformin and sulfonylurea therapy in type 2 diabetes mellitus (LEAD-5 met+SU): a randomised controlled trial.
    Diabetologia, 2009, Volume: 52, Issue:10

    Topics: Adolescent; Adult; Aged; Aged, 80 and over; Blood Glucose; Body Weight; Diabetes Mellitus, Type 2; D

2009
Liraglutide vs insulin glargine and placebo in combination with metformin and sulfonylurea therapy in type 2 diabetes mellitus (LEAD-5 met+SU): a randomised controlled trial.
    Diabetologia, 2009, Volume: 52, Issue:10

    Topics: Adolescent; Adult; Aged; Aged, 80 and over; Blood Glucose; Body Weight; Diabetes Mellitus, Type 2; D

2009
Liraglutide vs insulin glargine and placebo in combination with metformin and sulfonylurea therapy in type 2 diabetes mellitus (LEAD-5 met+SU): a randomised controlled trial.
    Diabetologia, 2009, Volume: 52, Issue:10

    Topics: Adolescent; Adult; Aged; Aged, 80 and over; Blood Glucose; Body Weight; Diabetes Mellitus, Type 2; D

2009
Initiation of prandial insulin therapy with AIR inhaled insulin or insulin lispro in patients with type 2 diabetes: A randomized noninferiority trial.
    Diabetes technology & therapeutics, 2009, Volume: 11 Suppl 2

    Topics: Administration, Inhalation; Aged; Body Mass Index; Body Weight; Diabetes Mellitus, Type 2; Drug Ther

2009
Pubertal metformin therapy to reduce total, visceral, and hepatic adiposity.
    The Journal of pediatrics, 2010, Volume: 156, Issue:1

    Topics: Adiposity; Adolescent; Body Weight; Child; Comorbidity; Female; Follow-Up Studies; Humans; Hyperinsu

2010
Effects of sitagliptin or metformin added to pioglitazone monotherapy in poorly controlled type 2 diabetes mellitus patients.
    Metabolism: clinical and experimental, 2010, Volume: 59, Issue:6

    Topics: Adiponectin; Blood Glucose; Body Weight; C-Reactive Protein; Diabetes Mellitus, Type 2; Diet; Double

2010
Effects of sitagliptin or metformin added to pioglitazone monotherapy in poorly controlled type 2 diabetes mellitus patients.
    Metabolism: clinical and experimental, 2010, Volume: 59, Issue:6

    Topics: Adiponectin; Blood Glucose; Body Weight; C-Reactive Protein; Diabetes Mellitus, Type 2; Diet; Double

2010
Effects of sitagliptin or metformin added to pioglitazone monotherapy in poorly controlled type 2 diabetes mellitus patients.
    Metabolism: clinical and experimental, 2010, Volume: 59, Issue:6

    Topics: Adiponectin; Blood Glucose; Body Weight; C-Reactive Protein; Diabetes Mellitus, Type 2; Diet; Double

2010
Effects of sitagliptin or metformin added to pioglitazone monotherapy in poorly controlled type 2 diabetes mellitus patients.
    Metabolism: clinical and experimental, 2010, Volume: 59, Issue:6

    Topics: Adiponectin; Blood Glucose; Body Weight; C-Reactive Protein; Diabetes Mellitus, Type 2; Diet; Double

2010
Baseline atherosclerosis parameter could assess the risk of bone loss during pioglitazone treatment in type 2 diabetes mellitus.
    Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA, 2010, Volume: 21, Issue:12

    Topics: Aged; Atherosclerosis; Biomarkers; Blood Glucose; Body Weight; Bone Density; Collagen; Diabetes Mell

2010
Exenatide versus glibenclamide in patients with diabetes.
    Diabetes technology & therapeutics, 2010, Volume: 12, Issue:3

    Topics: Adolescent; Adult; Aged; Aged, 80 and over; Blood Glucose; Body Mass Index; Body Weight; C-Reactive

2010
The effect of comprehensive lifestyle intervention or metformin on obesity in young women.
    Nutrition, metabolism, and cardiovascular diseases : NMCD, 2011, Volume: 21, Issue:4

    Topics: Adolescent; Adult; Behavior Therapy; Body Composition; Body Mass Index; Body Weight; Double-Blind Me

2011
Effects of the peroxisome proliferator-activated receptor (PPAR)-gamma agonist pioglitazone on renal and hormonal responses to salt in diabetic and hypertensive individuals.
    Diabetologia, 2010, Volume: 53, Issue:8

    Topics: Analysis of Variance; Blood Pressure; Body Weight; Cross-Over Studies; Diabetes Mellitus, Type 2; Do

2010
Metformin 2,500 mg/day in the treatment of obese women with polycystic ovary syndrome and its effect on weight, hormones, and lipid profile.
    Archives of gynecology and obstetrics, 2010, Volume: 282, Issue:6

    Topics: Adult; Body Weight; Female; Hormones; Humans; Hypoglycemic Agents; Lipids; Metformin; Obesity; Polyc

2010
Metformin and placebo therapy both improve weight management and fasting insulin in obese insulin-resistant adolescents: a prospective, placebo-controlled, randomized study.
    European journal of endocrinology, 2010, Volume: 163, Issue:4

    Topics: Adolescent; Body Mass Index; Body Weight; Child; Female; Humans; Hypoglycemic Agents; Insulin; Insul

2010
Vildagliptin add-on to metformin produces similar efficacy and reduced hypoglycaemic risk compared with glimepiride, with no weight gain: results from a 2-year study.
    Diabetes, obesity & metabolism, 2010, Volume: 12, Issue:9

    Topics: Adamantane; Adolescent; Adult; Aged; Body Weight; Diabetes Mellitus, Type 2; Double-Blind Method; Dr

2010
Benefits of self-monitoring blood glucose in the management of new-onset Type 2 diabetes mellitus: the St Carlos Study, a prospective randomized clinic-based interventional study with parallel groups.
    Journal of diabetes, 2010, Volume: 2, Issue:3

    Topics: Blood Glucose Self-Monitoring; Blood Pressure; Body Mass Index; Body Weight; Diabetes Mellitus, Type

2010
Pharmacological treatment of the pathogenetic defects in type 2 diabetes: the randomized multicenter South Danish Diabetes Study.
    Diabetes care, 2011, Volume: 34, Issue:1

    Topics: Adult; Aged; Blood Glucose; Body Weight; Diabetes Mellitus, Type 2; Female; Glycated Hemoglobin; Hum

2011
Use of twice-daily exenatide in Basal insulin-treated patients with type 2 diabetes: a randomized, controlled trial.
    Annals of internal medicine, 2011, Jan-18, Volume: 154, Issue:2

    Topics: Aged; Body Weight; Diabetes Mellitus, Type 2; Double-Blind Method; Drug Administration Schedule; Dru

2011
Effects of metformin on body weight and body composition in obese insulin-resistant children: a randomized clinical trial.
    Diabetes, 2011, Volume: 60, Issue:2

    Topics: Body Composition; Body Weight; Child; Double-Blind Method; Female; Humans; Hypoglycemic Agents; Insu

2011
The effects of metformin or orlistat on obese women with polycystic ovary syndrome: a prospective randomized open-label study.
    Journal of assisted reproduction and genetics, 2011, Volume: 28, Issue:7

    Topics: Adult; Anti-Obesity Agents; Body Mass Index; Body Weight; Female; Humans; Hypoglycemic Agents; Lacto

2011
Exenatide or glimepiride added to metformin on metabolic control and on insulin resistance in type 2 diabetic patients.
    European journal of pharmacology, 2011, Volume: 666, Issue:1-3

    Topics: Biomarkers; Blood Glucose; Body Mass Index; Body Weight; Diabetes Mellitus, Type 2; Exenatide; Femal

2011
Effects of combined exenatide and pioglitazone therapy on hepatic fat content in type 2 diabetes.
    Obesity (Silver Spring, Md.), 2011, Volume: 19, Issue:12

    Topics: Adiponectin; Adipose Tissue; Alanine Transaminase; Aspartate Aminotransferases; Biomarkers; Blood Gl

2011
Effects of exenatide on measures of β-cell function after 3 years in metformin-treated patients with type 2 diabetes.
    Diabetes care, 2011, Volume: 34, Issue:9

    Topics: Adult; Aged; Blood Glucose; Body Weight; C-Peptide; Diabetes Mellitus, Type 2; Exenatide; Female; Gl

2011
Exenatide decreases hepatic fibroblast growth factor 21 resistance in non-alcoholic fatty liver disease in a mouse model of obesity and in a randomised controlled trial.
    Diabetologia, 2011, Volume: 54, Issue:12

    Topics: Adult; Aged; Animals; Body Weight; Diabetes Mellitus, Type 2; Disease Models, Animal; Drug Therapy,

2011
Effects of acarbose versus glibenclamide on glycemic excursion and oxidative stress in type 2 diabetic patients inadequately controlled by metformin: a 24-week, randomized, open-label, parallel-group comparison.
    Clinical therapeutics, 2011, Volume: 33, Issue:12

    Topics: Acarbose; Adult; Aged; Biomarkers; Blood Glucose; Body Weight; Diabetes Mellitus, Type 2; Dinoprost;

2011
Effects of acarbose versus glibenclamide on glycemic excursion and oxidative stress in type 2 diabetic patients inadequately controlled by metformin: a 24-week, randomized, open-label, parallel-group comparison.
    Clinical therapeutics, 2011, Volume: 33, Issue:12

    Topics: Acarbose; Adult; Aged; Biomarkers; Blood Glucose; Body Weight; Diabetes Mellitus, Type 2; Dinoprost;

2011
Effects of acarbose versus glibenclamide on glycemic excursion and oxidative stress in type 2 diabetic patients inadequately controlled by metformin: a 24-week, randomized, open-label, parallel-group comparison.
    Clinical therapeutics, 2011, Volume: 33, Issue:12

    Topics: Acarbose; Adult; Aged; Biomarkers; Blood Glucose; Body Weight; Diabetes Mellitus, Type 2; Dinoprost;

2011
Effects of acarbose versus glibenclamide on glycemic excursion and oxidative stress in type 2 diabetic patients inadequately controlled by metformin: a 24-week, randomized, open-label, parallel-group comparison.
    Clinical therapeutics, 2011, Volume: 33, Issue:12

    Topics: Acarbose; Adult; Aged; Biomarkers; Blood Glucose; Body Weight; Diabetes Mellitus, Type 2; Dinoprost;

2011
Appropriate insulin initiation dosage for insulin-naive type 2 diabetes outpatients receiving insulin monotherapy or in combination with metformin and/or pioglitazone.
    Chinese medical journal, 2010, Volume: 123, Issue:24

    Topics: Adult; Aged; Blood Glucose; Body Weight; Diabetes Mellitus, Type 2; Drug Therapy, Combination; Femal

2010
Genetic predictors of weight loss and weight regain after intensive lifestyle modification, metformin treatment, or standard care in the Diabetes Prevention Program.
    Diabetes care, 2012, Volume: 35, Issue:2

    Topics: Alpha-Ketoglutarate-Dependent Dioxygenase FTO; Body Weight; Brain-Derived Neurotrophic Factor; Cell

2012
Effects of dapagliflozin on body weight, total fat mass, and regional adipose tissue distribution in patients with type 2 diabetes mellitus with inadequate glycemic control on metformin.
    The Journal of clinical endocrinology and metabolism, 2012, Volume: 97, Issue:3

    Topics: Adipose Tissue; Adult; Aged; Benzhydryl Compounds; Blood Glucose; Body Fat Distribution; Body Mass I

2012
Effects of dapagliflozin on body weight, total fat mass, and regional adipose tissue distribution in patients with type 2 diabetes mellitus with inadequate glycemic control on metformin.
    The Journal of clinical endocrinology and metabolism, 2012, Volume: 97, Issue:3

    Topics: Adipose Tissue; Adult; Aged; Benzhydryl Compounds; Blood Glucose; Body Fat Distribution; Body Mass I

2012
Effects of dapagliflozin on body weight, total fat mass, and regional adipose tissue distribution in patients with type 2 diabetes mellitus with inadequate glycemic control on metformin.
    The Journal of clinical endocrinology and metabolism, 2012, Volume: 97, Issue:3

    Topics: Adipose Tissue; Adult; Aged; Benzhydryl Compounds; Blood Glucose; Body Fat Distribution; Body Mass I

2012
Effects of dapagliflozin on body weight, total fat mass, and regional adipose tissue distribution in patients with type 2 diabetes mellitus with inadequate glycemic control on metformin.
    The Journal of clinical endocrinology and metabolism, 2012, Volume: 97, Issue:3

    Topics: Adipose Tissue; Adult; Aged; Benzhydryl Compounds; Blood Glucose; Body Fat Distribution; Body Mass I

2012
Effects of dapagliflozin on body weight, total fat mass, and regional adipose tissue distribution in patients with type 2 diabetes mellitus with inadequate glycemic control on metformin.
    The Journal of clinical endocrinology and metabolism, 2012, Volume: 97, Issue:3

    Topics: Adipose Tissue; Adult; Aged; Benzhydryl Compounds; Blood Glucose; Body Fat Distribution; Body Mass I

2012
Effects of dapagliflozin on body weight, total fat mass, and regional adipose tissue distribution in patients with type 2 diabetes mellitus with inadequate glycemic control on metformin.
    The Journal of clinical endocrinology and metabolism, 2012, Volume: 97, Issue:3

    Topics: Adipose Tissue; Adult; Aged; Benzhydryl Compounds; Blood Glucose; Body Fat Distribution; Body Mass I

2012
Effects of dapagliflozin on body weight, total fat mass, and regional adipose tissue distribution in patients with type 2 diabetes mellitus with inadequate glycemic control on metformin.
    The Journal of clinical endocrinology and metabolism, 2012, Volume: 97, Issue:3

    Topics: Adipose Tissue; Adult; Aged; Benzhydryl Compounds; Blood Glucose; Body Fat Distribution; Body Mass I

2012
Effects of dapagliflozin on body weight, total fat mass, and regional adipose tissue distribution in patients with type 2 diabetes mellitus with inadequate glycemic control on metformin.
    The Journal of clinical endocrinology and metabolism, 2012, Volume: 97, Issue:3

    Topics: Adipose Tissue; Adult; Aged; Benzhydryl Compounds; Blood Glucose; Body Fat Distribution; Body Mass I

2012
Effects of dapagliflozin on body weight, total fat mass, and regional adipose tissue distribution in patients with type 2 diabetes mellitus with inadequate glycemic control on metformin.
    The Journal of clinical endocrinology and metabolism, 2012, Volume: 97, Issue:3

    Topics: Adipose Tissue; Adult; Aged; Benzhydryl Compounds; Blood Glucose; Body Fat Distribution; Body Mass I

2012
Effects of dapagliflozin on body weight, total fat mass, and regional adipose tissue distribution in patients with type 2 diabetes mellitus with inadequate glycemic control on metformin.
    The Journal of clinical endocrinology and metabolism, 2012, Volume: 97, Issue:3

    Topics: Adipose Tissue; Adult; Aged; Benzhydryl Compounds; Blood Glucose; Body Fat Distribution; Body Mass I

2012
Effects of dapagliflozin on body weight, total fat mass, and regional adipose tissue distribution in patients with type 2 diabetes mellitus with inadequate glycemic control on metformin.
    The Journal of clinical endocrinology and metabolism, 2012, Volume: 97, Issue:3

    Topics: Adipose Tissue; Adult; Aged; Benzhydryl Compounds; Blood Glucose; Body Fat Distribution; Body Mass I

2012
Effects of dapagliflozin on body weight, total fat mass, and regional adipose tissue distribution in patients with type 2 diabetes mellitus with inadequate glycemic control on metformin.
    The Journal of clinical endocrinology and metabolism, 2012, Volume: 97, Issue:3

    Topics: Adipose Tissue; Adult; Aged; Benzhydryl Compounds; Blood Glucose; Body Fat Distribution; Body Mass I

2012
Effects of dapagliflozin on body weight, total fat mass, and regional adipose tissue distribution in patients with type 2 diabetes mellitus with inadequate glycemic control on metformin.
    The Journal of clinical endocrinology and metabolism, 2012, Volume: 97, Issue:3

    Topics: Adipose Tissue; Adult; Aged; Benzhydryl Compounds; Blood Glucose; Body Fat Distribution; Body Mass I

2012
Effects of dapagliflozin on body weight, total fat mass, and regional adipose tissue distribution in patients with type 2 diabetes mellitus with inadequate glycemic control on metformin.
    The Journal of clinical endocrinology and metabolism, 2012, Volume: 97, Issue:3

    Topics: Adipose Tissue; Adult; Aged; Benzhydryl Compounds; Blood Glucose; Body Fat Distribution; Body Mass I

2012
Effects of dapagliflozin on body weight, total fat mass, and regional adipose tissue distribution in patients with type 2 diabetes mellitus with inadequate glycemic control on metformin.
    The Journal of clinical endocrinology and metabolism, 2012, Volume: 97, Issue:3

    Topics: Adipose Tissue; Adult; Aged; Benzhydryl Compounds; Blood Glucose; Body Fat Distribution; Body Mass I

2012
Effects of dapagliflozin on body weight, total fat mass, and regional adipose tissue distribution in patients with type 2 diabetes mellitus with inadequate glycemic control on metformin.
    The Journal of clinical endocrinology and metabolism, 2012, Volume: 97, Issue:3

    Topics: Adipose Tissue; Adult; Aged; Benzhydryl Compounds; Blood Glucose; Body Fat Distribution; Body Mass I

2012
Effects of dapagliflozin on body weight, total fat mass, and regional adipose tissue distribution in patients with type 2 diabetes mellitus with inadequate glycemic control on metformin.
    The Journal of clinical endocrinology and metabolism, 2012, Volume: 97, Issue:3

    Topics: Adipose Tissue; Adult; Aged; Benzhydryl Compounds; Blood Glucose; Body Fat Distribution; Body Mass I

2012
Effects of dapagliflozin on body weight, total fat mass, and regional adipose tissue distribution in patients with type 2 diabetes mellitus with inadequate glycemic control on metformin.
    The Journal of clinical endocrinology and metabolism, 2012, Volume: 97, Issue:3

    Topics: Adipose Tissue; Adult; Aged; Benzhydryl Compounds; Blood Glucose; Body Fat Distribution; Body Mass I

2012
Effects of dapagliflozin on body weight, total fat mass, and regional adipose tissue distribution in patients with type 2 diabetes mellitus with inadequate glycemic control on metformin.
    The Journal of clinical endocrinology and metabolism, 2012, Volume: 97, Issue:3

    Topics: Adipose Tissue; Adult; Aged; Benzhydryl Compounds; Blood Glucose; Body Fat Distribution; Body Mass I

2012
Effects of dapagliflozin on body weight, total fat mass, and regional adipose tissue distribution in patients with type 2 diabetes mellitus with inadequate glycemic control on metformin.
    The Journal of clinical endocrinology and metabolism, 2012, Volume: 97, Issue:3

    Topics: Adipose Tissue; Adult; Aged; Benzhydryl Compounds; Blood Glucose; Body Fat Distribution; Body Mass I

2012
Effects of dapagliflozin on body weight, total fat mass, and regional adipose tissue distribution in patients with type 2 diabetes mellitus with inadequate glycemic control on metformin.
    The Journal of clinical endocrinology and metabolism, 2012, Volume: 97, Issue:3

    Topics: Adipose Tissue; Adult; Aged; Benzhydryl Compounds; Blood Glucose; Body Fat Distribution; Body Mass I

2012
Effects of dapagliflozin on body weight, total fat mass, and regional adipose tissue distribution in patients with type 2 diabetes mellitus with inadequate glycemic control on metformin.
    The Journal of clinical endocrinology and metabolism, 2012, Volume: 97, Issue:3

    Topics: Adipose Tissue; Adult; Aged; Benzhydryl Compounds; Blood Glucose; Body Fat Distribution; Body Mass I

2012
Effects of dapagliflozin on body weight, total fat mass, and regional adipose tissue distribution in patients with type 2 diabetes mellitus with inadequate glycemic control on metformin.
    The Journal of clinical endocrinology and metabolism, 2012, Volume: 97, Issue:3

    Topics: Adipose Tissue; Adult; Aged; Benzhydryl Compounds; Blood Glucose; Body Fat Distribution; Body Mass I

2012
Effects of dapagliflozin on body weight, total fat mass, and regional adipose tissue distribution in patients with type 2 diabetes mellitus with inadequate glycemic control on metformin.
    The Journal of clinical endocrinology and metabolism, 2012, Volume: 97, Issue:3

    Topics: Adipose Tissue; Adult; Aged; Benzhydryl Compounds; Blood Glucose; Body Fat Distribution; Body Mass I

2012
Effects of dapagliflozin on body weight, total fat mass, and regional adipose tissue distribution in patients with type 2 diabetes mellitus with inadequate glycemic control on metformin.
    The Journal of clinical endocrinology and metabolism, 2012, Volume: 97, Issue:3

    Topics: Adipose Tissue; Adult; Aged; Benzhydryl Compounds; Blood Glucose; Body Fat Distribution; Body Mass I

2012
Metformin for treatment of antipsychotic-induced weight gain: a randomized, placebo-controlled study.
    Schizophrenia research, 2012, Volume: 138, Issue:1

    Topics: Adult; Antipsychotic Agents; Blood Glucose; Body Mass Index; Body Weight; Double-Blind Method; Femal

2012
Dapagliflozin, metformin XR, or both: initial pharmacotherapy for type 2 diabetes, a randomised controlled trial.
    International journal of clinical practice, 2012, Volume: 66, Issue:5

    Topics: Adolescent; Adult; Aged; Benzhydryl Compounds; Blood Glucose; Body Weight; Diabetes Mellitus, Type 2

2012
Dapagliflozin, metformin XR, or both: initial pharmacotherapy for type 2 diabetes, a randomised controlled trial.
    International journal of clinical practice, 2012, Volume: 66, Issue:5

    Topics: Adolescent; Adult; Aged; Benzhydryl Compounds; Blood Glucose; Body Weight; Diabetes Mellitus, Type 2

2012
Dapagliflozin, metformin XR, or both: initial pharmacotherapy for type 2 diabetes, a randomised controlled trial.
    International journal of clinical practice, 2012, Volume: 66, Issue:5

    Topics: Adolescent; Adult; Aged; Benzhydryl Compounds; Blood Glucose; Body Weight; Diabetes Mellitus, Type 2

2012
Dapagliflozin, metformin XR, or both: initial pharmacotherapy for type 2 diabetes, a randomised controlled trial.
    International journal of clinical practice, 2012, Volume: 66, Issue:5

    Topics: Adolescent; Adult; Aged; Benzhydryl Compounds; Blood Glucose; Body Weight; Diabetes Mellitus, Type 2

2012
Glycemic control over 5 years in 4,900 people with type 2 diabetes: real-world diabetes therapy in a clinical trial cohort.
    Diabetes care, 2012, Volume: 35, Issue:5

    Topics: Aged; Blood Glucose; Body Weight; Diabetes Mellitus, Type 2; Female; Humans; Hypoglycemic Agents; In

2012
Long-term effects of adding exenatide to a regimen of metformin and/or sulfonylurea in type 2 diabetes: an uncontrolled, open-label trial in Hungary.
    Clinical therapeutics, 2012, Volume: 34, Issue:6

    Topics: Blood Glucose; Body Weight; Diabetes Mellitus, Type 2; Drug Therapy, Combination; Exenatide; Female;

2012
Insulin glargine versus sitagliptin in insulin-naive patients with type 2 diabetes mellitus uncontrolled on metformin (EASIE): a multicentre, randomised open-label trial.
    Lancet (London, England), 2012, Jun-16, Volume: 379, Issue:9833

    Topics: Adult; Aged; Body Weight; Diabetes Mellitus, Type 2; Female; Glycated Hemoglobin; Humans; Hypoglycem

2012
Metformin for treatment of antipsychotic-induced amenorrhea and weight gain in women with first-episode schizophrenia: a double-blind, randomized, placebo-controlled study.
    The American journal of psychiatry, 2012, Volume: 169, Issue:8

    Topics: Adolescent; Adult; Amenorrhea; Antipsychotic Agents; Blood Glucose; Body Mass Index; Body Weight; Do

2012
Comparing the efficacy and safety profile of sitagliptin versus glimepiride in patients of type 2 diabetes mellitus inadequately controlled with metformin alone.
    The Journal of the Association of Physicians of India, 2012, Volume: 60

    Topics: Body Weight; Diabetes Mellitus, Type 2; Dipeptidyl-Peptidase IV Inhibitors; Dose-Response Relationsh

2012
Efficacy and safety of switching from the DPP-4 inhibitor sitagliptin to the human GLP-1 analog liraglutide after 52 weeks in metformin-treated patients with type 2 diabetes: a randomized, open-label trial.
    Diabetes care, 2012, Volume: 35, Issue:10

    Topics: Adult; Blood Glucose; Body Weight; Diabetes Mellitus, Type 2; Dipeptidyl-Peptidase IV Inhibitors; Gl

2012
Improved glycaemic control with vildagliptin added to insulin, with or without metformin, in patients with type 2 diabetes mellitus.
    Diabetes, obesity & metabolism, 2013, Volume: 15, Issue:3

    Topics: Adamantane; Adolescent; Adult; Aged; Aged, 80 and over; Asia; Australia; Blood Glucose; Body Weight;

2013
Treatment with pioglitazone is associated with decreased preprandial ghrelin levels: a randomized clinical trial.
    Peptides, 2013, Volume: 40

    Topics: Adult; Blood Glucose; Body Weight; Diabetes Mellitus, Type 2; Female; Ghrelin; Glucose Tolerance Tes

2013
A Phase IIb, randomized, placebo-controlled study of the SGLT2 inhibitor empagliflozin in patients with type 2 diabetes.
    Diabetes, obesity & metabolism, 2013, Volume: 15, Issue:8

    Topics: Adult; Aged; Aged, 80 and over; Argentina; Benzhydryl Compounds; Blood Glucose; Body Weight; Diabete

2013
A Phase IIb, randomized, placebo-controlled study of the SGLT2 inhibitor empagliflozin in patients with type 2 diabetes.
    Diabetes, obesity & metabolism, 2013, Volume: 15, Issue:8

    Topics: Adult; Aged; Aged, 80 and over; Argentina; Benzhydryl Compounds; Blood Glucose; Body Weight; Diabete

2013
A Phase IIb, randomized, placebo-controlled study of the SGLT2 inhibitor empagliflozin in patients with type 2 diabetes.
    Diabetes, obesity & metabolism, 2013, Volume: 15, Issue:8

    Topics: Adult; Aged; Aged, 80 and over; Argentina; Benzhydryl Compounds; Blood Glucose; Body Weight; Diabete

2013
A Phase IIb, randomized, placebo-controlled study of the SGLT2 inhibitor empagliflozin in patients with type 2 diabetes.
    Diabetes, obesity & metabolism, 2013, Volume: 15, Issue:8

    Topics: Adult; Aged; Aged, 80 and over; Argentina; Benzhydryl Compounds; Blood Glucose; Body Weight; Diabete

2013
A Phase IIb, randomized, placebo-controlled study of the SGLT2 inhibitor empagliflozin in patients with type 2 diabetes.
    Diabetes, obesity & metabolism, 2013, Volume: 15, Issue:8

    Topics: Adult; Aged; Aged, 80 and over; Argentina; Benzhydryl Compounds; Blood Glucose; Body Weight; Diabete

2013
A Phase IIb, randomized, placebo-controlled study of the SGLT2 inhibitor empagliflozin in patients with type 2 diabetes.
    Diabetes, obesity & metabolism, 2013, Volume: 15, Issue:8

    Topics: Adult; Aged; Aged, 80 and over; Argentina; Benzhydryl Compounds; Blood Glucose; Body Weight; Diabete

2013
A Phase IIb, randomized, placebo-controlled study of the SGLT2 inhibitor empagliflozin in patients with type 2 diabetes.
    Diabetes, obesity & metabolism, 2013, Volume: 15, Issue:8

    Topics: Adult; Aged; Aged, 80 and over; Argentina; Benzhydryl Compounds; Blood Glucose; Body Weight; Diabete

2013
A Phase IIb, randomized, placebo-controlled study of the SGLT2 inhibitor empagliflozin in patients with type 2 diabetes.
    Diabetes, obesity & metabolism, 2013, Volume: 15, Issue:8

    Topics: Adult; Aged; Aged, 80 and over; Argentina; Benzhydryl Compounds; Blood Glucose; Body Weight; Diabete

2013
A Phase IIb, randomized, placebo-controlled study of the SGLT2 inhibitor empagliflozin in patients with type 2 diabetes.
    Diabetes, obesity & metabolism, 2013, Volume: 15, Issue:8

    Topics: Adult; Aged; Aged, 80 and over; Argentina; Benzhydryl Compounds; Blood Glucose; Body Weight; Diabete

2013
[The efficacy and safety of pioglitazone hydrochloride in combination with sulphonylureas and metfomin in the treatment of type 2 diabetes mellitus a 12-week randomized multi-centres placebo-controlled parallel study].
    Zhonghua nei ke za zhi, 2002, Volume: 41, Issue:6

    Topics: Blood Pressure; Body Weight; Cholesterol; Consumer Product Safety; Diabetes Mellitus, Type 2; Dose-R

2002
Improved glycaemic control with metformin-glibenclamide combined tablet therapy (Glucovance) in Type 2 diabetic patients inadequately controlled on metformin.
    Diabetic medicine : a journal of the British Diabetic Association, 2002, Volume: 19, Issue:8

    Topics: Blood Glucose; Body Weight; Diabetes Mellitus, Type 2; Dose-Response Relationship, Drug; Double-Blin

2002
The effect of metformin on hirsutism in polycystic ovary syndrome.
    European journal of endocrinology, 2002, Volume: 147, Issue:2

    Topics: Body Constitution; Body Height; Body Weight; Double-Blind Method; Female; Hair; Hirsutism; Humans; H

2002
Rosiglitazone but not metformin enhances insulin- and exercise-stimulated skeletal muscle glucose uptake in patients with newly diagnosed type 2 diabetes.
    Diabetes, 2002, Volume: 51, Issue:12

    Topics: Blood Glucose; Body Weight; Diabetes Mellitus, Type 2; Dose-Response Relationship, Drug; Exercise; F

2002
A randomized trial of sibutramine in the management of obese type 2 diabetic patients treated with metformin.
    Diabetes care, 2003, Volume: 26, Issue:1

    Topics: Appetite Depressants; Blood Glucose; Blood Pressure; Body Weight; Cyclobutanes; Diabetes Mellitus; D

2003
Differential effects of rosiglitazone and metformin on adipose tissue distribution and glucose uptake in type 2 diabetic subjects.
    Diabetes, 2003, Volume: 52, Issue:2

    Topics: Adipose Tissue; Aged; Blood Glucose; Body Weight; Diabetes Mellitus, Type 2; Female; Fluorodeoxygluc

2003
Effect on glycemic control of exenatide (synthetic exendin-4) additive to existing metformin and/or sulfonylurea treatment in patients with type 2 diabetes.
    Diabetes care, 2003, Volume: 26, Issue:8

    Topics: Blood Glucose; Blood Pressure; Body Weight; Diabetes Mellitus, Type 2; Drug Therapy, Combination; Ex

2003
Efficacy of glyburide/metformin tablets compared with initial monotherapy in type 2 diabetes.
    The Journal of clinical endocrinology and metabolism, 2003, Volume: 88, Issue:8

    Topics: Adult; Aged; Blood Glucose; Body Weight; Diabetes Mellitus, Type 2; Double-Blind Method; Drug Combin

2003
Efficacy, tolerability and safety of nateglinide in combination with metformin. Results from a study under general practice conditions.
    Experimental and clinical endocrinology & diabetes : official journal, German Society of Endocrinology [and] German Diabetes Association, 2003, Volume: 111, Issue:5

    Topics: Adult; Aged; Aged, 80 and over; Blood Glucose; Blood Pressure; Body Weight; Cyclohexanes; Diabetes M

2003
Metformin therapy increases insulin-stimulated release of D-chiro-inositol-containing inositolphosphoglycan mediator in women with polycystic ovary syndrome.
    The Journal of clinical endocrinology and metabolism, 2004, Volume: 89, Issue:1

    Topics: Adolescent; Adult; Area Under Curve; Body Mass Index; Body Weight; Female; Glucose Tolerance Test; H

2004
Effect of metformin treatment on multiple cardiovascular disease risk factors in patients with type 2 diabetes mellitus.
    Metabolism: clinical and experimental, 2004, Volume: 53, Issue:2

    Topics: Aged; Blood Glucose; Blood Pressure; Body Weight; Cardiovascular Diseases; Cholesterol; Diabetes Mel

2004
Nonobese women with polycystic ovary syndrome respond better than obese women to treatment with metformin.
    Fertility and sterility, 2004, Volume: 81, Issue:2

    Topics: Administration, Oral; Adult; Body Mass Index; Body Weight; Double-Blind Method; Female; Hormones; Hu

2004
Effects of a combination of recombinant human growth hormone with metformin on glucose metabolism and body composition in patients with metabolic syndrome.
    Hormone and metabolic research = Hormon- und Stoffwechselforschung = Hormones et metabolisme, 2004, Volume: 36, Issue:1

    Topics: Aged; Arginine; Blood Glucose; Blood Pressure; Body Composition; Body Constitution; Body Weight; Dia

2004
Metformin during pregnancy reduces insulin, insulin resistance, insulin secretion, weight, testosterone and development of gestational diabetes: prospective longitudinal assessment of women with polycystic ovary syndrome from preconception throughout preg
    Human reproduction (Oxford, England), 2004, Volume: 19, Issue:3

    Topics: Adult; Body Weight; Cohort Studies; Diabetes, Gestational; Female; Humans; Hypoglycemic Agents; Insu

2004
Effect of pramlintide on weight in overweight and obese insulin-treated type 2 diabetes patients.
    Obesity research, 2004, Volume: 12, Issue:4

    Topics: Aged; Amyloid; Body Mass Index; Body Weight; Diabetes Mellitus; Diabetes Mellitus, Type 2; Double-Bl

2004
Height, weight, and motor-social development during the first 18 months of life in 126 infants born to 109 mothers with polycystic ovary syndrome who conceived on and continued metformin through pregnancy.
    Human reproduction (Oxford, England), 2004, Volume: 19, Issue:6

    Topics: Adult; Body Height; Body Weight; Child Development; Diabetes, Gestational; Female; Humans; Hypoglyce

2004
Improved glycemic control without weight gain using triple therapy in type 2 diabetes.
    Diabetes care, 2004, Volume: 27, Issue:7

    Topics: Blood Glucose; Body Weight; Diabetes Mellitus, Type 2; Drug Therapy, Combination; Ethnicity; Female;

2004
Effect of metformin vs. placebo treatment on serum fatty acids in non-diabetic obese insulin resistant individuals.
    Prostaglandins, leukotrienes, and essential fatty acids, 2004, Volume: 71, Issue:6

    Topics: Adult; Anthropometry; Body Mass Index; Body Weight; Diabetes Mellitus, Type 2; Double-Blind Method;

2004
Orlistat is as beneficial as metformin in the treatment of polycystic ovarian syndrome.
    The Journal of clinical endocrinology and metabolism, 2005, Volume: 90, Issue:2

    Topics: Adult; Blood Pressure; Body Mass Index; Body Weight; Cholesterol; Enzyme Inhibitors; Female; Humans;

2005
Homocysteine levels in women with polycystic ovary syndrome treated with metformin versus rosiglitazone: a randomized study.
    Human reproduction (Oxford, England), 2005, Volume: 20, Issue:4

    Topics: Adult; Anovulation; Blood Glucose; Body Weight; Female; Folic Acid; Homocysteine; Humans; Hypoglycem

2005
Initiating insulin therapy in type 2 Diabetes: a comparison of biphasic and basal insulin analogs.
    Diabetes care, 2005, Volume: 28, Issue:2

    Topics: Adult; Blood Glucose; Body Weight; Diabetes Mellitus, Type 2; Drug Therapy, Combination; Female; Gly

2005
Comparison of effect of pioglitazone with metformin or sulfonylurea (monotherapy and combination therapy) on postload glycemia and composite insulin sensitivity index during an oral glucose tolerance test in patients with type 2 diabetes.
    Diabetes care, 2005, Volume: 28, Issue:2

    Topics: Adult; Aged; Blood Glucose; Body Weight; Diabetes Mellitus, Type 2; Drug Therapy, Combination; Femal

2005
Administration of B-group vitamins reduces circulating homocysteine in polycystic ovarian syndrome patients treated with metformin: a randomized trial.
    Human reproduction (Oxford, England), 2005, Volume: 20, Issue:6

    Topics: Adolescent; Adult; Blood Glucose; Body Weight; Dose-Response Relationship, Drug; Female; Folic Acid;

2005
Effects of exenatide (exendin-4) on glycemic control over 30 weeks in patients with type 2 diabetes treated with metformin and a sulfonylurea.
    Diabetes care, 2005, Volume: 28, Issue:5

    Topics: Adult; Aged; Blood Glucose; Body Weight; Diabetes Mellitus, Type 2; Drug Therapy, Combination; Exena

2005
Effects of exenatide (exendin-4) on glycemic control and weight over 30 weeks in metformin-treated patients with type 2 diabetes.
    Diabetes care, 2005, Volume: 28, Issue:5

    Topics: Adult; Aged; Blood Glucose; Body Weight; Diabetes Mellitus, Type 2; Drug Therapy, Combination; Exena

2005
Effects of exenatide (exendin-4) on glycemic control and weight over 30 weeks in metformin-treated patients with type 2 diabetes.
    Diabetes care, 2005, Volume: 28, Issue:5

    Topics: Adult; Aged; Blood Glucose; Body Weight; Diabetes Mellitus, Type 2; Drug Therapy, Combination; Exena

2005
Effects of exenatide (exendin-4) on glycemic control and weight over 30 weeks in metformin-treated patients with type 2 diabetes.
    Diabetes care, 2005, Volume: 28, Issue:5

    Topics: Adult; Aged; Blood Glucose; Body Weight; Diabetes Mellitus, Type 2; Drug Therapy, Combination; Exena

2005
Effects of exenatide (exendin-4) on glycemic control and weight over 30 weeks in metformin-treated patients with type 2 diabetes.
    Diabetes care, 2005, Volume: 28, Issue:5

    Topics: Adult; Aged; Blood Glucose; Body Weight; Diabetes Mellitus, Type 2; Drug Therapy, Combination; Exena

2005
Safety and tolerability of pioglitazone, metformin, and gliclazide in the treatment of type 2 diabetes.
    Diabetes research and clinical practice, 2005, Volume: 70, Issue:1

    Topics: Adult; Aged; Alanine Transaminase; Alkaline Phosphatase; Aspartate Aminotransferases; Blood Glucose;

2005
Role of insulin secretion and sensitivity in the evolution of type 2 diabetes in the diabetes prevention program: effects of lifestyle intervention and metformin.
    Diabetes, 2005, Volume: 54, Issue:8

    Topics: Adult; Blood Glucose; Body Weight; Diabetes Mellitus, Type 2; Fasting; Female; Glucose Tolerance Tes

2005
Role of insulin secretion and sensitivity in the evolution of type 2 diabetes in the diabetes prevention program: effects of lifestyle intervention and metformin.
    Diabetes, 2005, Volume: 54, Issue:8

    Topics: Adult; Blood Glucose; Body Weight; Diabetes Mellitus, Type 2; Fasting; Female; Glucose Tolerance Tes

2005
Role of insulin secretion and sensitivity in the evolution of type 2 diabetes in the diabetes prevention program: effects of lifestyle intervention and metformin.
    Diabetes, 2005, Volume: 54, Issue:8

    Topics: Adult; Blood Glucose; Body Weight; Diabetes Mellitus, Type 2; Fasting; Female; Glucose Tolerance Tes

2005
Role of insulin secretion and sensitivity in the evolution of type 2 diabetes in the diabetes prevention program: effects of lifestyle intervention and metformin.
    Diabetes, 2005, Volume: 54, Issue:8

    Topics: Adult; Blood Glucose; Body Weight; Diabetes Mellitus, Type 2; Fasting; Female; Glucose Tolerance Tes

2005
The effects of rosiglitazone and metformin on oxidative stress and homocysteine levels in lean patients with polycystic ovary syndrome.
    Human reproduction (Oxford, England), 2005, Volume: 20, Issue:12

    Topics: Adult; Androgens; Antioxidants; Blood Glucose; Body Mass Index; Body Weight; Female; Homeostasis; Ho

2005
Biphasic insulin aspart 30 plus metformin: an effective combination in type 2 diabetes.
    Diabetes, obesity & metabolism, 2006, Volume: 8, Issue:1

    Topics: Biphasic Insulins; Blood Glucose; Body Weight; Diabetes Mellitus, Type 2; Drug Administration Schedu

2006
Comparative efficacy of glimepiride and/or metformin with insulin in type 2 diabetes.
    Diabetes research and clinical practice, 2006, Volume: 72, Issue:3

    Topics: Aged; Blood Glucose; Body Mass Index; Body Weight; Chemotherapy, Adjuvant; Diabetes Mellitus, Type 2

2006
Metformin-glibenclamide versus metformin plus rosiglitazone in patients with type 2 diabetes inadequately controlled on metformin monotherapy.
    Diabetes, obesity & metabolism, 2006, Volume: 8, Issue:2

    Topics: Adult; Aged; Blood Glucose; Body Weight; Diabetes Mellitus, Type 2; Double-Blind Method; Drug Combin

2006
Insulin glargine or NPH combined with metformin in type 2 diabetes: the LANMET study.
    Diabetologia, 2006, Volume: 49, Issue:3

    Topics: Adult; Aged; Blood Glucose; Body Weight; Diabetes Mellitus, Type 2; Drug Therapy, Combination; Fasti

2006
Insulin glargine or NPH combined with metformin in type 2 diabetes: the LANMET study.
    Diabetologia, 2006, Volume: 49, Issue:3

    Topics: Adult; Aged; Blood Glucose; Body Weight; Diabetes Mellitus, Type 2; Drug Therapy, Combination; Fasti

2006
Insulin glargine or NPH combined with metformin in type 2 diabetes: the LANMET study.
    Diabetologia, 2006, Volume: 49, Issue:3

    Topics: Adult; Aged; Blood Glucose; Body Weight; Diabetes Mellitus, Type 2; Drug Therapy, Combination; Fasti

2006
Insulin glargine or NPH combined with metformin in type 2 diabetes: the LANMET study.
    Diabetologia, 2006, Volume: 49, Issue:3

    Topics: Adult; Aged; Blood Glucose; Body Weight; Diabetes Mellitus, Type 2; Drug Therapy, Combination; Fasti

2006
Insulin glargine or NPH combined with metformin in type 2 diabetes: the LANMET study.
    Diabetologia, 2006, Volume: 49, Issue:3

    Topics: Adult; Aged; Blood Glucose; Body Weight; Diabetes Mellitus, Type 2; Drug Therapy, Combination; Fasti

2006
Insulin glargine or NPH combined with metformin in type 2 diabetes: the LANMET study.
    Diabetologia, 2006, Volume: 49, Issue:3

    Topics: Adult; Aged; Blood Glucose; Body Weight; Diabetes Mellitus, Type 2; Drug Therapy, Combination; Fasti

2006
Insulin glargine or NPH combined with metformin in type 2 diabetes: the LANMET study.
    Diabetologia, 2006, Volume: 49, Issue:3

    Topics: Adult; Aged; Blood Glucose; Body Weight; Diabetes Mellitus, Type 2; Drug Therapy, Combination; Fasti

2006
Insulin glargine or NPH combined with metformin in type 2 diabetes: the LANMET study.
    Diabetologia, 2006, Volume: 49, Issue:3

    Topics: Adult; Aged; Blood Glucose; Body Weight; Diabetes Mellitus, Type 2; Drug Therapy, Combination; Fasti

2006
Insulin glargine or NPH combined with metformin in type 2 diabetes: the LANMET study.
    Diabetologia, 2006, Volume: 49, Issue:3

    Topics: Adult; Aged; Blood Glucose; Body Weight; Diabetes Mellitus, Type 2; Drug Therapy, Combination; Fasti

2006
Interim analysis of the effects of exenatide treatment on A1C, weight and cardiovascular risk factors over 82 weeks in 314 overweight patients with type 2 diabetes.
    Diabetes, obesity & metabolism, 2006, Volume: 8, Issue:4

    Topics: Adolescent; Adult; Aged; Blood Glucose; Blood Pressure; Body Weight; Cardiovascular Diseases; Diabet

2006
Interim analysis of the effects of exenatide treatment on A1C, weight and cardiovascular risk factors over 82 weeks in 314 overweight patients with type 2 diabetes.
    Diabetes, obesity & metabolism, 2006, Volume: 8, Issue:4

    Topics: Adolescent; Adult; Aged; Blood Glucose; Blood Pressure; Body Weight; Cardiovascular Diseases; Diabet

2006
Interim analysis of the effects of exenatide treatment on A1C, weight and cardiovascular risk factors over 82 weeks in 314 overweight patients with type 2 diabetes.
    Diabetes, obesity & metabolism, 2006, Volume: 8, Issue:4

    Topics: Adolescent; Adult; Aged; Blood Glucose; Blood Pressure; Body Weight; Cardiovascular Diseases; Diabet

2006
Interim analysis of the effects of exenatide treatment on A1C, weight and cardiovascular risk factors over 82 weeks in 314 overweight patients with type 2 diabetes.
    Diabetes, obesity & metabolism, 2006, Volume: 8, Issue:4

    Topics: Adolescent; Adult; Aged; Blood Glucose; Blood Pressure; Body Weight; Cardiovascular Diseases; Diabet

2006
Insulin sensitivity during oral glucose tolerance test and its relations to parameters of glucose metabolism and endothelial function in type 2 diabetic subjects under metformin and thiazolidinedione.
    Diabetes, obesity & metabolism, 2006, Volume: 8, Issue:5

    Topics: Blood Glucose; Body Weight; C-Peptide; Cell Adhesion Molecules; Chromans; Diabetes Mellitus, Type 2;

2006
Five weeks of treatment with the GLP-1 analogue liraglutide improves glycaemic control and lowers body weight in subjects with type 2 diabetes.
    Experimental and clinical endocrinology & diabetes : official journal, German Society of Endocrinology [and] German Diabetes Association, 2006, Volume: 114, Issue:8

    Topics: Adult; Blood Glucose; Body Weight; Diabetes Mellitus, Type 2; Double-Blind Method; Drug Therapy, Com

2006
Starting insulin therapy in type 2 diabetes: twice-daily biphasic insulin Aspart 30 plus metformin versus once-daily insulin glargine plus glimepiride.
    Experimental and clinical endocrinology & diabetes : official journal, German Society of Endocrinology [and] German Diabetes Association, 2006, Volume: 114, Issue:9

    Topics: Aged; Biphasic Insulins; Blood Glucose; Body Weight; Diabetes Mellitus, Type 2; Dose-Response Relati

2006
Changes in weight, papilledema, headache, visual field, and life status in response to diet and metformin in women with idiopathic intracranial hypertension with and without concurrent polycystic ovary syndrome or hyperinsulinemia.
    Translational research : the journal of laboratory and clinical medicine, 2006, Volume: 148, Issue:5

    Topics: Adolescent; Adult; Body Mass Index; Body Weight; Combined Modality Therapy; Diet, Reducing; Female;

2006
Oral antidiabetic drugs: bioavailability assessment of fixed-dose combination tablets of pioglitazone and metformin. Effect of body weight, gender, and race on systemic exposures of each drug.
    Journal of clinical pharmacology, 2007, Volume: 47, Issue:1

    Topics: Administration, Oral; Adult; Area Under Curve; Biological Availability; Black People; Body Weight; D

2007
Effect of metformin on serum lipoprotein lipase mass levels and LDL particle size in type 2 diabetes mellitus patients.
    Diabetes research and clinical practice, 2007, Volume: 78, Issue:1

    Topics: Blood Glucose; Body Weight; Diabetes Mellitus, Type 2; Drug Therapy, Combination; Female; Glycated H

2007
Targeting hyperglycaemia with either metformin or repaglinide in non-obese patients with type 2 diabetes: results from a randomized crossover trial.
    Diabetes, obesity & metabolism, 2007, Volume: 9, Issue:3

    Topics: Adiponectin; Biomarkers; Blood Glucose; Body Weight; C-Peptide; C-Reactive Protein; Carbamates; Cros

2007
Comparison of two doses of metformin (2.5 and 1.5 g/day) for the treatment of polycystic ovary syndrome and their effect on body mass index and waist circumference.
    Fertility and sterility, 2007, Volume: 88, Issue:2

    Topics: Adult; Body Mass Index; Body Weight; Dose-Response Relationship, Drug; Drug Administration Schedule;

2007
Metformin as an adjunctive treatment to control body weight and metabolic dysfunction during olanzapine administration: a multicentric, double-blind, placebo-controlled trial.
    Schizophrenia research, 2007, Volume: 93, Issue:1-3

    Topics: Adult; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Blood Glucose; Body Mass Index; Body

2007
Insulin sensitivity after metformin suspension in normal-weight women with polycystic ovary syndrome.
    The Journal of clinical endocrinology and metabolism, 2007, Volume: 92, Issue:8

    Topics: Adult; Area Under Curve; Body Mass Index; Body Weight; Female; Glucose Clamp Technique; Hormones; Hu

2007
Metformin in normal-weight hirsute women with polycystic ovary syndrome with normal insulin sensitivity.
    Gynecological endocrinology : the official journal of the International Society of Gynecological Endocrinology, 2007, Volume: 23, Issue:5

    Topics: Adolescent; Adult; Blood Glucose; Body Weight; Female; Hirsutism; Hormones; Humans; Hypoglycemic Age

2007
Prevention of gestational diabetes by metformin plus diet in patients with polycystic ovary syndrome.
    Fertility and sterility, 2008, Volume: 89, Issue:3

    Topics: Adult; Blood Glucose; Body Weight; Diabetes, Gestational; Female; Humans; Hypoglycemic Agents; Insul

2008
Efficacy of metformin in obese and non-obese women with polycystic ovary syndrome: a randomized, double-blinded, placebo-controlled cross-over trial.
    Human reproduction (Oxford, England), 2007, Volume: 22, Issue:11

    Topics: Adolescent; Adult; Body Weight; Cross-Over Studies; Double-Blind Method; Female; Humans; Insulin; Me

2007
Metformin reduces thyrotropin levels in obese, diabetic women with primary hypothyroidism on thyroxine replacement therapy.
    Endocrine, 2007, Volume: 32, Issue:1

    Topics: Aged; Body Weight; Diabetes Mellitus, Type 2; Female; Glycated Hemoglobin; Humans; Hypoglycemic Agen

2007
Efficacy and tolerability of vildagliptin vs. pioglitazone when added to metformin: a 24-week, randomized, double-blind study.
    Diabetes, obesity & metabolism, 2008, Volume: 10, Issue:1

    Topics: Adamantane; Adolescent; Adult; Aged; Blood Glucose; Body Weight; Diabetes Mellitus, Type 2; Double-B

2008
Metformin for metabolic dysregulation in schizophrenic patients treated with olanzapine.
    Progress in neuro-psychopharmacology & biological psychiatry, 2008, May-15, Volume: 32, Issue:4

    Topics: Adolescent; Adult; Antipsychotic Agents; Benzodiazepines; Blood Glucose; Body Weight; Female; Glucos

2008
Tolerability and efficacy of exenatide and titrated insulin glargine in adult patients with type 2 diabetes previously uncontrolled with metformin or a sulfonylurea: a multinational, randomized, open-label, two-period, crossover noninferiority trial.
    Clinical therapeutics, 2007, Volume: 29, Issue:11

    Topics: Adult; Blood Glucose; Body Weight; Cross-Over Studies; Diabetes Mellitus, Type 2; Double-Blind Metho

2007
Efficacy and safety of sitagliptin added to ongoing metformin therapy in patients with type 2 diabetes.
    Current medical research and opinion, 2008, Volume: 24, Issue:2

    Topics: Adult; Aged; Area Under Curve; Body Weight; Diabetes Mellitus, Type 2; Drug Therapy, Combination; Fe

2008
Efficacy and safety of sitagliptin when added to ongoing metformin therapy in patients with type 2 diabetes.
    Diabetes, obesity & metabolism, 2008, Volume: 10, Issue:10

    Topics: Analysis of Variance; Biomarkers; Blood Glucose; Body Weight; Cholesterol, LDL; Diabetes Mellitus, T

2008
Efficacy and safety of sitagliptin when added to ongoing metformin therapy in patients with type 2 diabetes.
    Diabetes, obesity & metabolism, 2008, Volume: 10, Issue:10

    Topics: Analysis of Variance; Biomarkers; Blood Glucose; Body Weight; Cholesterol, LDL; Diabetes Mellitus, T

2008
Efficacy and safety of sitagliptin when added to ongoing metformin therapy in patients with type 2 diabetes.
    Diabetes, obesity & metabolism, 2008, Volume: 10, Issue:10

    Topics: Analysis of Variance; Biomarkers; Blood Glucose; Body Weight; Cholesterol, LDL; Diabetes Mellitus, T

2008
Efficacy and safety of sitagliptin when added to ongoing metformin therapy in patients with type 2 diabetes.
    Diabetes, obesity & metabolism, 2008, Volume: 10, Issue:10

    Topics: Analysis of Variance; Biomarkers; Blood Glucose; Body Weight; Cholesterol, LDL; Diabetes Mellitus, T

2008
Efficacy and safety of sitagliptin when added to ongoing metformin therapy in patients with type 2 diabetes.
    Diabetes, obesity & metabolism, 2008, Volume: 10, Issue:10

    Topics: Analysis of Variance; Biomarkers; Blood Glucose; Body Weight; Cholesterol, LDL; Diabetes Mellitus, T

2008
Efficacy and safety of sitagliptin when added to ongoing metformin therapy in patients with type 2 diabetes.
    Diabetes, obesity & metabolism, 2008, Volume: 10, Issue:10

    Topics: Analysis of Variance; Biomarkers; Blood Glucose; Body Weight; Cholesterol, LDL; Diabetes Mellitus, T

2008
Efficacy and safety of sitagliptin when added to ongoing metformin therapy in patients with type 2 diabetes.
    Diabetes, obesity & metabolism, 2008, Volume: 10, Issue:10

    Topics: Analysis of Variance; Biomarkers; Blood Glucose; Body Weight; Cholesterol, LDL; Diabetes Mellitus, T

2008
Efficacy and safety of sitagliptin when added to ongoing metformin therapy in patients with type 2 diabetes.
    Diabetes, obesity & metabolism, 2008, Volume: 10, Issue:10

    Topics: Analysis of Variance; Biomarkers; Blood Glucose; Body Weight; Cholesterol, LDL; Diabetes Mellitus, T

2008
Efficacy and safety of sitagliptin when added to ongoing metformin therapy in patients with type 2 diabetes.
    Diabetes, obesity & metabolism, 2008, Volume: 10, Issue:10

    Topics: Analysis of Variance; Biomarkers; Blood Glucose; Body Weight; Cholesterol, LDL; Diabetes Mellitus, T

2008
Metformin, but not pioglitazone, decreases postchallenge plasma ghrelin levels in type 2 diabetic patients: a possible role in weight stability?
    Diabetes, obesity & metabolism, 2008, Volume: 10, Issue:11

    Topics: Area Under Curve; Blood Glucose; Body Mass Index; Body Weight; Diabetes Mellitus, Type 2; Female; Gh

2008
The metabolic effects of once daily extended-release metformin in patients with type 2 diabetes: a multicentre study.
    International journal of clinical practice, 2008, Volume: 62, Issue:5

    Topics: Adult; Aged; Blood Glucose; Body Weight; Delayed-Action Preparations; Diabetes Mellitus, Type 2; Fem

2008
Impact of metformin versus repaglinide on non-glycaemic cardiovascular risk markers related to inflammation and endothelial dysfunction in non-obese patients with type 2 diabetes.
    European journal of endocrinology, 2008, Volume: 158, Issue:5

    Topics: Aged; Blood Glucose; Body Weight; Carbamates; Cross-Over Studies; Diabetes Mellitus, Type 2; Diabeti

2008
Comparison of single and combined treatment with exenatide and metformin on menstrual cyclicity in overweight women with polycystic ovary syndrome.
    The Journal of clinical endocrinology and metabolism, 2008, Volume: 93, Issue:7

    Topics: Adiponectin; Adult; Body Weight; Drug Therapy, Combination; Exenatide; Female; Humans; Lipids; Menst

2008
Comparison of single and combined treatment with exenatide and metformin on menstrual cyclicity in overweight women with polycystic ovary syndrome.
    The Journal of clinical endocrinology and metabolism, 2008, Volume: 93, Issue:7

    Topics: Adiponectin; Adult; Body Weight; Drug Therapy, Combination; Exenatide; Female; Humans; Lipids; Menst

2008
Comparison of single and combined treatment with exenatide and metformin on menstrual cyclicity in overweight women with polycystic ovary syndrome.
    The Journal of clinical endocrinology and metabolism, 2008, Volume: 93, Issue:7

    Topics: Adiponectin; Adult; Body Weight; Drug Therapy, Combination; Exenatide; Female; Humans; Lipids; Menst

2008
Comparison of single and combined treatment with exenatide and metformin on menstrual cyclicity in overweight women with polycystic ovary syndrome.
    The Journal of clinical endocrinology and metabolism, 2008, Volume: 93, Issue:7

    Topics: Adiponectin; Adult; Body Weight; Drug Therapy, Combination; Exenatide; Female; Humans; Lipids; Menst

2008
Comparison of single and combined treatment with exenatide and metformin on menstrual cyclicity in overweight women with polycystic ovary syndrome.
    The Journal of clinical endocrinology and metabolism, 2008, Volume: 93, Issue:7

    Topics: Adiponectin; Adult; Body Weight; Drug Therapy, Combination; Exenatide; Female; Humans; Lipids; Menst

2008
Comparison of single and combined treatment with exenatide and metformin on menstrual cyclicity in overweight women with polycystic ovary syndrome.
    The Journal of clinical endocrinology and metabolism, 2008, Volume: 93, Issue:7

    Topics: Adiponectin; Adult; Body Weight; Drug Therapy, Combination; Exenatide; Female; Humans; Lipids; Menst

2008
Comparison of single and combined treatment with exenatide and metformin on menstrual cyclicity in overweight women with polycystic ovary syndrome.
    The Journal of clinical endocrinology and metabolism, 2008, Volume: 93, Issue:7

    Topics: Adiponectin; Adult; Body Weight; Drug Therapy, Combination; Exenatide; Female; Humans; Lipids; Menst

2008
Comparison of single and combined treatment with exenatide and metformin on menstrual cyclicity in overweight women with polycystic ovary syndrome.
    The Journal of clinical endocrinology and metabolism, 2008, Volume: 93, Issue:7

    Topics: Adiponectin; Adult; Body Weight; Drug Therapy, Combination; Exenatide; Female; Humans; Lipids; Menst

2008
Comparison of single and combined treatment with exenatide and metformin on menstrual cyclicity in overweight women with polycystic ovary syndrome.
    The Journal of clinical endocrinology and metabolism, 2008, Volume: 93, Issue:7

    Topics: Adiponectin; Adult; Body Weight; Drug Therapy, Combination; Exenatide; Female; Humans; Lipids; Menst

2008
Ciclazindol: an oral agent with weight reducing properties and hypoglycaemic activity.
    European journal of clinical pharmacology, 1983, Volume: 25, Issue:1

    Topics: Adult; Aged; Appetite Depressants; Body Weight; Diabetes Mellitus; Female; Glucose Tolerance Test; H

1983
Efficacy of metformin in patients with non-insulin-dependent diabetes mellitus. The Multicenter Metformin Study Group.
    The New England journal of medicine, 1995, Aug-31, Volume: 333, Issue:9

    Topics: Blood Glucose; Body Weight; Cholesterol; Diabetes Mellitus; Diabetes Mellitus, Type 2; Double-Blind

1995
Efficacy of metformin in patients with non-insulin-dependent diabetes mellitus. The Multicenter Metformin Study Group.
    The New England journal of medicine, 1995, Aug-31, Volume: 333, Issue:9

    Topics: Blood Glucose; Body Weight; Cholesterol; Diabetes Mellitus; Diabetes Mellitus, Type 2; Double-Blind

1995
Efficacy of metformin in patients with non-insulin-dependent diabetes mellitus. The Multicenter Metformin Study Group.
    The New England journal of medicine, 1995, Aug-31, Volume: 333, Issue:9

    Topics: Blood Glucose; Body Weight; Cholesterol; Diabetes Mellitus; Diabetes Mellitus, Type 2; Double-Blind

1995
Efficacy of metformin in patients with non-insulin-dependent diabetes mellitus. The Multicenter Metformin Study Group.
    The New England journal of medicine, 1995, Aug-31, Volume: 333, Issue:9

    Topics: Blood Glucose; Body Weight; Cholesterol; Diabetes Mellitus; Diabetes Mellitus, Type 2; Double-Blind

1995
Efficacy of metformin in patients with non-insulin-dependent diabetes mellitus. The Multicenter Metformin Study Group.
    The New England journal of medicine, 1995, Aug-31, Volume: 333, Issue:9

    Topics: Blood Glucose; Body Weight; Cholesterol; Diabetes Mellitus; Diabetes Mellitus, Type 2; Double-Blind

1995
Efficacy of metformin in patients with non-insulin-dependent diabetes mellitus. The Multicenter Metformin Study Group.
    The New England journal of medicine, 1995, Aug-31, Volume: 333, Issue:9

    Topics: Blood Glucose; Body Weight; Cholesterol; Diabetes Mellitus; Diabetes Mellitus, Type 2; Double-Blind

1995
Efficacy of metformin in patients with non-insulin-dependent diabetes mellitus. The Multicenter Metformin Study Group.
    The New England journal of medicine, 1995, Aug-31, Volume: 333, Issue:9

    Topics: Blood Glucose; Body Weight; Cholesterol; Diabetes Mellitus; Diabetes Mellitus, Type 2; Double-Blind

1995
Efficacy of metformin in patients with non-insulin-dependent diabetes mellitus. The Multicenter Metformin Study Group.
    The New England journal of medicine, 1995, Aug-31, Volume: 333, Issue:9

    Topics: Blood Glucose; Body Weight; Cholesterol; Diabetes Mellitus; Diabetes Mellitus, Type 2; Double-Blind

1995
Efficacy of metformin in patients with non-insulin-dependent diabetes mellitus. The Multicenter Metformin Study Group.
    The New England journal of medicine, 1995, Aug-31, Volume: 333, Issue:9

    Topics: Blood Glucose; Body Weight; Cholesterol; Diabetes Mellitus; Diabetes Mellitus, Type 2; Double-Blind

1995
Therapeutic comparison of metformin and sulfonylurea, alone and in various combinations. A double-blind controlled study.
    Diabetes care, 1994, Volume: 17, Issue:10

    Topics: Adult; Aged; Blood Glucose; Blood Pressure; Body Weight; C-Peptide; Diabetes Mellitus, Type 2; Drug

1994
United Kingdom Prospective Diabetes Study (UKPDS). 13: Relative efficacy of randomly allocated diet, sulphonylurea, insulin, or metformin in patients with newly diagnosed non-insulin dependent diabetes followed for three years.
    BMJ (Clinical research ed.), 1995, Jan-14, Volume: 310, Issue:6972

    Topics: Adult; Aged; Blood Glucose; Body Weight; Chlorpropamide; Diabetes Mellitus; Diabetes Mellitus, Type

1995
Metformin and metoprolol CR treatment in non-obese men.
    Journal of internal medicine, 1994, Volume: 235, Issue:4

    Topics: Analysis of Variance; Anthropometry; Blood Pressure; Body Weight; Delayed-Action Preparations; Doubl

1994
Comparison between acarbose, metformin, and insulin treatment in type 2 diabetic patients with secondary failure to sulfonylurea treatment.
    Diabete & metabolisme, 1995, Volume: 21, Issue:4

    Topics: Acarbose; Aged; Blood Glucose; Blood Pressure; Body Mass Index; Body Weight; Cholesterol; Cholestero

1995
Improvement of insulin sensitivity by metformin treatment does not lower blood pressure of nonobese insulin-resistant hypertensive patients with normal glucose tolerance.
    The Journal of clinical endocrinology and metabolism, 1996, Volume: 81, Issue:4

    Topics: Adult; Aged; Alanine; Aldosterone; Blood Glucose; Blood Pressure; Body Weight; Cross-Over Studies; D

1996
The effects of high- and medium-dose metformin therapy on cardiovascular risk factors in patients with type II diabetes.
    Diabetes care, 1996, Volume: 19, Issue:1

    Topics: Analysis of Variance; Blood Glucose; Blood Pressure; Body Weight; Cardiovascular Diseases; Cholester

1996
Metformin improves blood lipid pattern in nondiabetic patients with coronary heart disease.
    Journal of internal medicine, 1996, Volume: 239, Issue:3

    Topics: Blood Glucose; Body Weight; Combined Modality Therapy; Coronary Disease; Diet; Humans; Hyperlipidemi

1996
Effects of metformin on the pathways of glucose utilization after oral glucose in non-insulin-dependent diabetes mellitus patients.
    Metabolism: clinical and experimental, 1997, Volume: 46, Issue:2

    Topics: Administration, Oral; Blood Glucose; Body Weight; Diabetes Mellitus, Type 2; Fasting; Glucose; Gluco

1997
The effects of metformin on glycemic control and serum lipids in insulin-treated NIDDM patients with suboptimal metabolic control.
    Diabetes care, 1998, Volume: 21, Issue:5

    Topics: Aged; Blood Glucose; Blood Pressure; Body Weight; Cholesterol; Cholesterol, HDL; Cholesterol, LDL; C

1998
Irreversibility of the defect in glycogen synthase activity in skeletal muscle from obese patients with NIDDM treated with diet and metformin.
    Diabetes care, 1998, Volume: 21, Issue:9

    Topics: Adult; Blood Glucose; Body Weight; Calorimetry, Indirect; Diabetes Mellitus; Diabetes Mellitus, Type

1998
Effects of metformin in patients with poorly controlled, insulin-treated type 2 diabetes mellitus. A randomized, double-blind, placebo-controlled trial.
    Annals of internal medicine, 1999, Aug-03, Volume: 131, Issue:3

    Topics: Blood Glucose; Body Weight; C-Peptide; Diabetes Mellitus, Type 2; Double-Blind Method; Drug Therapy,

1999
A comparison of preconstituted, fixed combinations of low-dose glyburide plus metformin versus high-dose glyburide alone in the treatment of type 2 diabetic patients.
    Acta diabetologica, 1999, Volume: 36, Issue:1-2

    Topics: Blood Glucose; Body Weight; C-Peptide; Cross-Over Studies; Diabetes Mellitus, Type 2; Double-Blind M

1999
A comparison of troglitazone and metformin on insulin requirements in euglycemic intensively insulin-treated type 2 diabetic patients.
    Diabetes, 1999, Volume: 48, Issue:12

    Topics: Blood Glucose; Body Weight; C-Peptide; Cholesterol; Cholesterol, HDL; Cholesterol, LDL; Chromans; Ci

1999
Intensive insulin therapy combined with metformin in obese type 2 diabetic patients.
    Acta diabetologica, 2000, Volume: 37, Issue:1

    Topics: Body Mass Index; Body Weight; C-Peptide; Cholesterol; Diabetes Mellitus; Diabetes Mellitus, Type 2;

2000
The effects of metformin on body mass index and glucose tolerance in obese adolescents with fasting hyperinsulinemia and a family history of type 2 diabetes.
    Pediatrics, 2001, Volume: 107, Issue:4

    Topics: Adolescent; Blood Glucose; Body Mass Index; Body Weight; Child; Comorbidity; Diabetes Mellitus; Diab

2001
Metabolic effects of metformin in patients with impaired glucose tolerance.
    Diabetic medicine : a journal of the British Diabetic Association, 2001, Volume: 18, Issue:7

    Topics: Blood Glucose; Blood Pressure; Body Weight; Diabetes Mellitus, Type 2; Energy Metabolism; Fatty Acid

2001
Vascular effects of glibenclamide vs. glimepiride and metformin in Type 2 diabetic patients.
    Diabetic medicine : a journal of the British Diabetic Association, 2002, Volume: 19, Issue:2

    Topics: Acetylcholine; Adult; Aged; Blood Flow Velocity; Blood Pressure; Body Mass Index; Body Weight; C-Pep

2002
Evaluation of the safety and efficacy of sibutramine, orlistat and metformin in the treatment of obesity.
    Diabetes, obesity & metabolism, 2002, Volume: 4, Issue:1

    Topics: Adult; Anti-Obesity Agents; Appetite Depressants; Blood Glucose; Body Mass Index; Body Weight; Cyclo

2002
Long-term glycaemic improvement after addition of metformin to insulin in insulin-treated obese type 2 diabetes patients.
    Diabetes, obesity & metabolism, 2001, Volume: 3, Issue:6

    Topics: Blood Glucose; Blood Pressure; Body Mass Index; Body Weight; Cholesterol; Diabetes Mellitus; Diabete

2001
Short-term treatment with metformin decreases serum leptin concentration without affecting body weight and body fat content in normal-weight healthy men.
    Metabolism: clinical and experimental, 2002, Volume: 51, Issue:4

    Topics: Adipose Tissue; Adult; Blood Pressure; Body Weight; C-Peptide; Diabetes Mellitus; Glucagon; Humans;

2002
Nateglinide improves glycaemic control when added to metformin monotherapy: results of a randomized trial with type 2 diabetes patients.
    Diabetes, obesity & metabolism, 2002, Volume: 4, Issue:3

    Topics: Aged; Blood Glucose; Body Mass Index; Body Weight; Cholesterol; Cyclohexanes; Diabetes Mellitus, Typ

2002
Simultaneous glyburide/metformin therapy is superior to component monotherapy as an initial pharmacological treatment for type 2 diabetes.
    Diabetes, obesity & metabolism, 2002, Volume: 4, Issue:3

    Topics: Blood Glucose; Body Weight; Diabetes Mellitus, Type 2; Drug Therapy, Combination; Fasting; Female; G

2002
Effect of orlistat in overweight and obese patients with type 2 diabetes treated with metformin.
    Diabetes care, 2002, Volume: 25, Issue:7

    Topics: Adult; Aged; Anti-Obesity Agents; Blood Glucose; Blood Pressure; Body Weight; Cholesterol; Diabetes

2002
Glipizide in the treatment of maturity-onset diabetes: a multi-centre, out-patient study.
    Current medical research and opinion, 1978, Volume: 5, Issue:5

    Topics: Adult; Aged; Blood Glucose; Body Weight; Clinical Trials as Topic; Diabetes Mellitus; Female; Glipiz

1978
Comparison of metformin and chlorpropamide in non-obese, maturity-onset diabetics uncontrolled by diet.
    British medical journal, 1977, Dec-17, Volume: 2, Issue:6102

    Topics: Administration, Oral; Adult; Age Factors; Aged; Body Weight; Chlorpropamide; Diabetes Mellitus; Diet

1977
[Therapy of diabetes mellitus using metformin. Clinical study on 60 patients].
    Die Medizinische Welt, 1975, Mar-14, Volume: 26, Issue:11

    Topics: Body Weight; Clinical Trials as Topic; Delayed-Action Preparations; Diabetes Mellitus; Drug Therapy,

1975
[Antidiabetic efficacy of benfluorex. Clinical data].
    Presse medicale (Paris, France : 1983), 1992, Sep-09, Volume: 21, Issue:28

    Topics: Blood Glucose; Body Weight; Diabetes Mellitus, Type 2; Female; Fenfluramine; Humans; Hypolipidemic A

1992
Comparison of combined therapies in treatment of secondary failure to glyburide.
    Diabetes care, 1992, Volume: 15, Issue:4

    Topics: Blood Glucose; Body Weight; C-Peptide; Diabetes Mellitus; Diabetes Mellitus, Type 2; Drug Administra

1992
Prospective comparative study in NIDDM patients of metformin and glibenclamide with special reference to lipid profiles.
    European journal of clinical pharmacology, 1991, Volume: 41, Issue:3

    Topics: Administration, Oral; Adult; Aged; Blood Glucose; Body Weight; C-Peptide; Cholesterol; Diabetes Mell

1991
Comparative three-month study of the efficacies of metformin and gliclazide in the treatment of NIDD.
    Diabete & metabolisme, 1991, Volume: 17, Issue:1 Pt 2

    Topics: Blood Glucose; Body Weight; Cholesterol; Diabetes Mellitus, Type 2; Fasting; Female; Gliclazide; Hum

1991
Double-blind evaluation of efficacy and tolerability of metformin in NIDDM.
    Diabetes care, 1991, Volume: 14, Issue:4

    Topics: Body Weight; Diabetes Mellitus, Type 2; Dose-Response Relationship, Drug; Double-Blind Method; Femal

1991
Comparison of tolbutamide and metformin in elderly diabetic patients.
    Diabetic medicine : a journal of the British Diabetic Association, 1990, Volume: 7, Issue:6

    Topics: Aged; Aged, 80 and over; Blood Glucose; Body Weight; Clinical Trials as Topic; Diabetes Mellitus, Ty

1990
Different effects of insulin and oral antidiabetic agents on glucose and energy metabolism in type 2 (non-insulin-dependent) diabetes mellitus.
    Diabetologia, 1989, Volume: 32, Issue:8

    Topics: Blood Glucose; Blood Glucose Self-Monitoring; Body Weight; Cholesterol; Diabetes Mellitus, Type 2; D

1989
Comparison of chlorpropamide and metformin treatment on weight and blood-glucose response of uncontrolled obese diabetics.
    Lancet (London, England), 1968, Jan-20, Volume: 1, Issue:7534

    Topics: Adult; Aged; Blood Glucose; Body Weight; Chlorpropamide; Diabetes Mellitus; Diet Therapy; Female; Hu

1968
Comparison of fenfluramine and metformin in treatment of obesity.
    Lancet (London, England), 1970, Aug-29, Volume: 2, Issue:7670

    Topics: Adult; Appetite Depressants; Body Weight; Clinical Trials as Topic; Female; Fenfluramine; Fluorine;

1970
Weight-reducing effect of diguanides in obese non-diabetic women.
    British medical journal, 1969, Apr-05, Volume: 2, Issue:5648

    Topics: Adult; Appetite; Bicarbonates; Body Weight; Clinical Trials as Topic; Female; Glucose Tolerance Test

1969
[Effect of metformin on glucose utilization and body weight].
    Deutsche medizinische Wochenschrift (1946), 1970, Oct-23, Volume: 95, Issue:43

    Topics: Biguanides; Blood Glucose; Body Weight; Glucose; Glucose Tolerance Test; Humans; Injections, Intrave

1970

Other Studies

323 other studies available for metformin and Body Weight

ArticleYear
Antihyperglycemic activity of phenolics from Pterocarpus marsupium.
    Journal of natural products, 1997, Volume: 60, Issue:6

    Topics: Animals; Benzofurans; Blood Glucose; Body Weight; Cresols; Diabetes Mellitus, Experimental; Female;

1997
Maprouneacin, a new daphnane diterpenoid with potent antihyperglycemic activity from Maprounea africana.
    Journal of natural products, 1999, Volume: 62, Issue:2

    Topics: Animals; Blood Glucose; Body Weight; Diabetes Mellitus, Type 2; Diterpenes; Feeding Behavior; Hypogl

1999
Antihyperglycemic sesquiterpenes from Psacalium decompositum.
    Journal of natural products, 1999, Volume: 62, Issue:8

    Topics: Animals; Asteraceae; Blood Glucose; Body Weight; Chromatography, High Pressure Liquid; Diabetes Mell

1999
Synthesis of novel triterpenoid (lupeol) derivatives and their in vivo antihyperglycemic and antidyslipidemic activity.
    Bioorganic & medicinal chemistry letters, 2009, Aug-01, Volume: 19, Issue:15

    Topics: Animals; Anti-Inflammatory Agents; Body Weight; Chemistry, Pharmaceutical; Cricetinae; Diabetes Mell

2009
Synthesis and biological evaluation of 5-benzylidenepyrimidine-2,4,6(1H,3H,5H)-trione derivatives for the treatment of obesity-related nonalcoholic fatty liver disease.
    Journal of medicinal chemistry, 2012, Nov-26, Volume: 55, Issue:22

    Topics: 3T3-L1 Cells; Adipocytes; Adiponectin; Alanine Transaminase; Animals; Barbiturates; Body Weight; Cho

2012
Discovery of tetrahydrocarbazoles with potent hypoglycemic and hypolipemic activities.
    European journal of medicinal chemistry, 2018, Apr-25, Volume: 150

    Topics: Blood Glucose; Body Weight; Carbazoles; Dose-Response Relationship, Drug; Drug Discovery; Hep G2 Cel

2018
Toward a treatment of diabesity: In vitro and in vivo evaluation of uncharged bromophenol derivatives as a new series of PTP1B inhibitors.
    European journal of medicinal chemistry, 2019, Mar-15, Volume: 166

    Topics: Animals; Body Weight; Cell Line; Diabetes Mellitus, Type 2; Drug Evaluation, Preclinical; Enzyme Inh

2019
Metformin and exenatide upregulate hepatocyte nuclear factor-4α, sex hormone binding globulin levels and improve hepatic triglyceride deposition in polycystic ovary syndrome with insulin resistance rats.
    The Journal of steroid biochemistry and molecular biology, 2021, Volume: 214

    Topics: Animals; Body Weight; Estrous Cycle; Exenatide; Female; Glucose Tolerance Test; Hepatocyte Nuclear F

2021
Coadministration of sitagliptin or metformin has no major impact on the adverse metabolic outcomes induced by dexamethasone treatment in rats.
    Life sciences, 2021, Dec-01, Volume: 286

    Topics: Animals; Blood Glucose; Body Weight; Dexamethasone; Diabetes Mellitus, Experimental; Feeding Behavio

2021
Maternal Metformin Treatment during Gestation and Lactation Improves Skeletal Muscle Development in Offspring of Rat Dams Fed High-Fat Diet.
    Nutrients, 2021, Sep-28, Volume: 13, Issue:10

    Topics: Animals; Biomarkers; Body Weight; Diet, High-Fat; Female; Gene Expression Regulation; Gestational Ag

2021
Morphological and functional characterization of diabetic cardiomyopathy in db/db mice following exercise, metformin alone, or combination treatments.
    Biochemical and biophysical research communications, 2021, 12-20, Volume: 584

    Topics: Animals; Blood Pressure; Body Weight; Combined Modality Therapy; Diabetes Mellitus, Type 2; Diabetic

2021
Metformin treatment of juvenile mice alters aging-related developmental and metabolic phenotypes.
    Mechanisms of ageing and development, 2022, Volume: 201

    Topics: Adiponectin; Age Factors; Aging; Animals; Body Weight; Feeding Behavior; Glucose Tolerance Test; Gro

2022
Comparison of Beinaglutide Versus Metformin for Weight Loss in Overweight and Obese Non-diabetic Patients.
    Experimental and clinical endocrinology & diabetes : official journal, German Society of Endocrinology [and] German Diabetes Association, 2022, Volume: 130, Issue:6

    Topics: Body Weight; Diabetes Mellitus, Type 2; Glucagon-Like Peptide 1; Humans; Hypoglycemic Agents; Metfor

2022
Dapagliflozin, metformin, monotherapy or both in patients with metabolic syndrome.
    Scientific reports, 2021, 12-20, Volume: 11, Issue:1

    Topics: Adult; Benzhydryl Compounds; Body Weight; C-Reactive Protein; Cholesterol, HDL; Diabetes Mellitus, T

2021
The Effects of Separate and Combined Treatment of Male Rats with Type 2 Diabetes with Metformin and Orthosteric and Allosteric Agonists of Luteinizing Hormone Receptor on Steroidogenesis and Spermatogenesis.
    International journal of molecular sciences, 2021, Dec-24, Volume: 23, Issue:1

    Topics: Adenylate Kinase; Allosteric Regulation; Animals; Area Under Curve; Blood Glucose; Body Weight; Diab

2021
Beneficial effects of metformin supplementation in hypothalamic paraventricular nucleus and arcuate nucleus of type 2 diabetic rats.
    Toxicology and applied pharmacology, 2022, 02-15, Volume: 437

    Topics: Animals; Arcuate Nucleus of Hypothalamus; Astrocytes; Blood Glucose; Body Weight; Diabetes Mellitus,

2022
Efficacy of tirzepatide 5, 10 and 15 mg versus semaglutide 2 mg in patients with type 2 diabetes: An adjusted indirect treatment comparison.
    Diabetes, obesity & metabolism, 2022, Volume: 24, Issue:9

    Topics: Body Weight; Diabetes Mellitus, Type 2; Double-Blind Method; Gastric Inhibitory Polypeptide; Glucago

2022
Predictors for successful weight reduction during treatment with Dapagliflozin among patients with type 2 diabetes mellitus in primary care.
    BMC primary care, 2022, 05-27, Volume: 23, Issue:1

    Topics: Benzhydryl Compounds; Body Weight; Diabetes Mellitus, Type 2; Female; Glucosides; Humans; Male; Metf

2022
Metformin, clomiphene citrate and flutamide effects on oocyte ultrastructure status and quality in PCOS mouse model.
    Reproductive biomedicine online, 2022, Volume: 45, Issue:2

    Topics: Animals; Body Weight; Clomiphene; Female; Fertility Agents, Female; Flutamide; Humans; Infertility,

2022
Linagliptin in Combination With Metformin Ameliorates Diabetic Osteoporosis Through Modulating BMP-2 and Sclerostin in the High-Fat Diet Fed C57BL/6 Mice.
    Frontiers in endocrinology, 2022, Volume: 13

    Topics: Animals; Biomarkers; Body Weight; Calcium; Cytokines; Diabetes Mellitus, Experimental; Diet, High-Fa

2022
Effect of Dapagliflozin in Combination with Lobeglitazone and Metformin in Korean Patients with Type 2 Diabetes in Real-World Clinical Practice.
    Yonsei medical journal, 2022, Volume: 63, Issue:9

    Topics: Benzhydryl Compounds; Blood Glucose; Body Weight; Diabetes Mellitus, Type 2; Double-Blind Method; Dr

2022
The consumption of sea buckthorn (Hippophae rhamnoides L.) effectively alleviates type 2 diabetes symptoms in spontaneous diabetic rats.
    Research in veterinary science, 2022, Dec-20, Volume: 152

    Topics: Animals; Antioxidants; Body Weight; Diabetes Mellitus, Experimental; Diabetes Mellitus, Type 2; Frui

2022
A Health Care Professional Delivered Low Carbohydrate Diet Program Reduces Body Weight, Haemoglobin A1c, Diabetes Medication Use and Cardiovascular Risk Markers-A Single-Arm Intervention Analysis.
    Nutrients, 2022, Oct-20, Volume: 14, Issue:20

    Topics: Adult; Body Weight; Cardiovascular Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 2; Diet, Car

2022
Combining Dietary Intervention with Metformin Treatment Enhances Non-Alcoholic Steatohepatitis Remission in Mice Fed a High-Fat High-Sucrose Diet.
    Biomolecules, 2022, 11-30, Volume: 12, Issue:12

    Topics: Animals; Body Weight; Diet, High-Fat; Insulin Resistance; Liver; Male; Metformin; Mice; Mice, Inbred

2022
Metformin improves polycystic ovary syndrome in mice by inhibiting ovarian ferroptosis.
    Frontiers in endocrinology, 2023, Volume: 14

    Topics: AMP-Activated Protein Kinases; Animals; Body Weight; Female; Ferroptosis; Humans; Insulin Resistance

2023
Therapeutic Potential of Metformin-preconditioned Mesenchymal Stem Cells for Pancreatic Regeneration.
    Current drug discovery technologies, 2023, Volume: 20, Issue:3

    Topics: Animals; Blood Glucose; Body Weight; Diabetes Mellitus, Experimental; Insulin; Mesenchymal Stem Cell

2023
Efficacy and safety of once-weekly efpeglenatide in people with suboptimally controlled type 2 diabetes: The AMPLITUDE-D, AMPLITUDE-L and AMPLITUDE-S randomized controlled trials.
    Diabetes, obesity & metabolism, 2023, Volume: 25, Issue:8

    Topics: Blood Glucose; Body Weight; Diabetes Mellitus, Type 2; Glucagon-Like Peptide 1; Glucagon-Like Peptid

2023
Metformin triggers a kidney GDF15-dependent area postrema axis to regulate food intake and body weight.
    Cell metabolism, 2023, 05-02, Volume: 35, Issue:5

    Topics: Animals; Area Postrema; Body Weight; Diabetes Mellitus, Type 2; Eating; Growth Differentiation Facto

2023
Vitamin D3 alleviates lung fibrosis of type 2 diabetic rats via SIRT3 mediated suppression of pyroptosis.
    Apoptosis : an international journal on programmed cell death, 2023, Volume: 28, Issue:11-12

    Topics: Animals; Apoptosis; Blood Glucose; Body Weight; Cholecalciferol; Diabetes Mellitus, Experimental; Di

2023
Dalbergiella welwitschia (Baker) Baker f. alkaloid-rich extracts attenuate liver damage in streptozotocin-induced diabetic rats.
    Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie, 2023, Volume: 168

    Topics: Alkaloids; Animals; Blood Glucose; Body Weight; Diabetes Mellitus, Experimental; Hypoglycemic Agents

2023
Metformin improves vascular and metabolic insulin action in insulin-resistant muscle.
    The Journal of endocrinology, 2019, Volume: 243, Issue:2

    Topics: Animals; Blood Flow Velocity; Blood Glucose; Body Weight; Diet, High-Fat; Femoral Artery; Glucose; G

2019
In uncontrolled type 2 diabetes, adjunctive semaglutide reduced HbA1c and body weight vs sitagliptin.
    Annals of internal medicine, 2019, 08-20, Volume: 171, Issue:4

    Topics: Adult; Body Weight; Diabetes Mellitus, Type 2; Glucagon-Like Peptides; Glycated Hemoglobin; Humans;

2019
Effect of high-fat diet-induced obesity on thyroid gland structure in female rats and the possible ameliorating effect of metformin therapy.
    Folia morphologica, 2020, Volume: 79, Issue:3

    Topics: Animals; Body Weight; Diet, High-Fat; Female; Hormones; Lipids; Metformin; Obesity; Rats; Thyroid Gl

2020
Effects of berberine and metformin on intestinal inflammation and gut microbiome composition in db/db mice.
    Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie, 2019, Volume: 118

    Topics: Animals; Berberine; Blood Glucose; Body Weight; Diabetes Mellitus, Experimental; Diabetes Mellitus,

2019
Letter to the Editor: Intrahepatic Lipid Content After Insulin Glargine Addition to Metformin in Type II Diabetes Mellitus With Nonalcoholic Fatty Liver Disease.
    Hepatology (Baltimore, Md.), 2020, Volume: 71, Issue:3

    Topics: Body Weight; Diabetes Mellitus, Type 2; Humans; Hypoglycemic Agents; Insulin Glargine; Lipids; Lirag

2020
Reply.
    Hepatology (Baltimore, Md.), 2020, Volume: 71, Issue:3

    Topics: Body Weight; Diabetes Mellitus, Type 2; Humans; Insulin Glargine; Lipids; Liraglutide; Metformin; No

2020
Intensification of medical management in type 2 diabetes: A real-world look at primary care practice.
    Journal of diabetes and its complications, 2020, Volume: 34, Issue:1

    Topics: Adolescent; Adult; Aged; Aged, 80 and over; Body Weight; Choice Behavior; Diabetes Mellitus, Type 2;

2020
Effect of Metformin on a Preeclampsia-Like Mouse Model Induced by High-Fat Diet.
    BioMed research international, 2019, Volume: 2019

    Topics: Animals; Blood Pressure; Body Weight; Diet, High-Fat; Disease Models, Animal; Female; Matrix Metallo

2019
Berberine attenuated olanzapine-induced metabolic alterations in mice: Targeting transient receptor potential vanilloid type 1 and 3 channels.
    Life sciences, 2020, Apr-15, Volume: 247

    Topics: Animals; Antipsychotic Agents; Berberine; Body Temperature; Body Weight; Cytokines; Drinking; Female

2020
Combined treatments with metformin and phosphodiesterase inhibitors alleviate nonalcoholic fatty liver disease in high-fat diet fed rats: a comparative study.
    Canadian journal of physiology and pharmacology, 2020, Volume: 98, Issue:8

    Topics: Alanine Transaminase; Animals; Aspartate Aminotransferases; Blood Glucose; Body Composition; Body We

2020
Comparative effects of glibenclamide, metformin and insulin on fetal pancreatic histology and maternal blood glucose in pregnant streptozotocin-induced diabetic rats.
    African health sciences, 2019, Volume: 19, Issue:3

    Topics: Animals; Blood Glucose; Body Weight; Diabetes Mellitus, Experimental; Diabetes, Gestational; Female;

2019
Exenatide ameliorates experimental non-alcoholic fatty liver in rats via suppression of toll-like receptor 4/NFκB signaling: Comparison to metformin.
    Life sciences, 2020, Jul-15, Volume: 253

    Topics: Animals; Body Weight; Diet, High-Fat; Disease Progression; Dose-Response Relationship, Drug; Exenati

2020
Effects of metformin on blood glucose levels and bodyweight mediated through intestinal effects.
    Journal of diabetes investigation, 2020, Volume: 11, Issue:6

    Topics: Blood Glucose; Body Weight; Diabetes Mellitus, Type 2; Humans; Hypoglycemic Agents; Intestinal Absor

2020
Metabolic benefits of annatto-extracted tocotrienol on glucose homeostasis, inflammation, and gut microbiome.
    Nutrition research (New York, N.Y.), 2020, Volume: 77

    Topics: Adipokines; Adipose Tissue, White; Animals; Bacteria; Bixaceae; Blood Glucose; Body Weight; Caroteno

2020
Combined use of Diane-35 and metformin improves the ovulation in the PCOS rat model possibly via regulating glycolysis pathway.
    Reproductive biology and endocrinology : RB&E, 2020, Jun-03, Volume: 18, Issue:1

    Topics: Androgen Antagonists; Animals; Apoptosis; Body Weight; Cyproterone Acetate; Disease Models, Animal;

2020
Combining a High Dose of Metformin With the SIRT1 Activator, SRT1720, Reduces Life Span in Aged Mice Fed a High-Fat Diet.
    The journals of gerontology. Series A, Biological sciences and medical sciences, 2020, 10-15, Volume: 75, Issue:11

    Topics: Animals; Body Composition; Body Weight; Diet, High-Fat; Heterocyclic Compounds, 4 or More Rings; Lon

2020
Glycemic Efficacy and Metabolic Consequences of an Empagliflozin Add-on versus Conventional Dose-Increasing Strategy in Patients with Type 2 Diabetes Inadequately Controlled by Metformin and Sulfonylurea.
    Endocrinology and metabolism (Seoul, Korea), 2020, Volume: 35, Issue:2

    Topics: Adult; Aged; Benzhydryl Compounds; Biomarkers; Blood Glucose; Blood Pressure; Body Mass Index; Body

2020
Metformin-induced increases in GDF15 are important for suppressing appetite and promoting weight loss.
    Nature metabolism, 2019, Volume: 1, Issue:12

    Topics: Animals; Appetite Depressants; Body Weight; Diabetes Mellitus, Type 2; Diet, High-Fat; Eating; Gluco

2019
Peanut skin extract ameliorates the symptoms of type 2 diabetes mellitus in mice by alleviating inflammation and maintaining gut microbiota homeostasis.
    Aging, 2020, 07-22, Volume: 12, Issue:14

    Topics: Animals; Anti-Inflammatory Agents; Arachis; Blood Glucose; Body Weight; Diabetes Mellitus, Type 2; E

2020
Metformin effectively restores the HPA axis function in diet-induced obese rats.
    International journal of obesity (2005), 2021, Volume: 45, Issue:2

    Topics: Animals; Body Weight; Corticosterone; Diet, High-Fat; Hypothalamo-Hypophyseal System; Male; Metformi

2021
Early metformin treatment improves pancreatic function and prevents metabolic dysfunction in early overfeeding male rats at adulthood.
    Experimental physiology, 2020, Volume: 105, Issue:12

    Topics: Adipose Tissue, White; Animals; Animals, Newborn; Blood Glucose; Body Composition; Body Weight; Fema

2020
Coadministration of metformin prevents olanzapine-induced metabolic dysfunction and regulates the gut-liver axis in rats.
    Psychopharmacology, 2021, Volume: 238, Issue:1

    Topics: Adjuvants, Pharmaceutic; Animals; Bacteroides; Blood Glucose; Body Weight; Dose-Response Relationshi

2021
Metformin alleviates allergic airway inflammation and increases Treg cells in obese asthma.
    Journal of cellular and molecular medicine, 2021, Volume: 25, Issue:4

    Topics: Animals; Anti-Inflammatory Agents; Asthma; Body Weight; Bronchoalveolar Lavage Fluid; CD4 Lymphocyte

2021
Effects of total flavonoids from Eucommia ulmoides Oliv. leaves on polycystic ovary syndrome with insulin resistance model rats induced by letrozole combined with a high-fat diet.
    Journal of ethnopharmacology, 2021, Jun-12, Volume: 273

    Topics: Animals; Body Weight; Diet, High-Fat; Disease Models, Animal; Eucommiaceae; Female; Flavonoids; Gona

2021
Comparative evaluation of metformin and liraglutide cardioprotective effect in rats with impaired glucose tolerance.
    Scientific reports, 2021, 03-23, Volume: 11, Issue:1

    Topics: Animals; Biomarkers; Blood Glucose; Body Weight; Cardiotonic Agents; Diabetes Mellitus, Experimental

2021
Metformin prevents stroke damage in non-diabetic female mice with chronic kidney disease.
    Scientific reports, 2021, 04-02, Volume: 11, Issue:1

    Topics: Adenylate Kinase; Animals; Apoptosis; Body Weight; Brain Infarction; Enzyme Activation; Female; Gene

2021
Associations between second-line glucose-lowering combination therapies with metformin and HbA1c, body weight, quality of life, hypoglycaemic events and glucose-lowering treatment intensification: The DISCOVER study.
    Diabetes, obesity & metabolism, 2021, Volume: 23, Issue:8

    Topics: Body Weight; Diabetes Mellitus, Type 2; Dipeptidyl-Peptidase IV Inhibitors; Drug Therapy, Combinatio

2021
DBPR108, a novel dipeptidyl peptidase-4 inhibitor with antihyperglycemic activity.
    Life sciences, 2021, Aug-01, Volume: 278

    Topics: Administration, Oral; Animals; Area Under Curve; Body Weight; Butanes; Diabetes Mellitus, Experiment

2021
Metabolic benefits of novel histamine H
    Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie, 2021, Volume: 142

    Topics: Adipose Tissue; Animals; Body Weight; C-Peptide; Carrier Proteins; Cholesterol; Energy Intake; Feedi

2021
Interaction of clozapine with metformin in a schizophrenia rat model.
    Scientific reports, 2021, 08-19, Volume: 11, Issue:1

    Topics: Animals; Behavior, Animal; Body Weight; Clozapine; Disease Models, Animal; Drug Interactions; Feedin

2021
Metformin and leucine increase satellite cells and collagen remodeling during disuse and recovery in aged muscle.
    FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 2021, Volume: 35, Issue:9

    Topics: Aging; AMP-Activated Protein Kinases; Animals; Body Weight; Collagen; Fibrosis; Hindlimb Suspension;

2021
Impact of health policy and practice on finding the best fit for patients with type 2 diabetes after metformin failure: Croatian pilot study.
    Primary care diabetes, 2017, Volume: 11, Issue:3

    Topics: Administration, Oral; Aged; Biomarkers; Blood Glucose; Body Mass Index; Body Weight; Clinical Decisi

2017
Metformin ameliorates hepatic steatosis and improves the induction of autophagy in HFD‑induced obese mice.
    Molecular medicine reports, 2017, Volume: 16, Issue:1

    Topics: Adipose Tissue; AMP-Activated Protein Kinases; Animals; Autophagy; Body Weight; Diet, High-Fat; Dise

2017
Diabetes-related weight change in a Canadian First Nation cohort.
    International journal of circumpolar health, 2017, Volume: 76, Issue:1

    Topics: Anthropometry; Body Weight; Cohort Studies; Diabetes Complications; Diabetes Mellitus, Type 2; Femal

2017
Effect of Dapagliflozin on Glycemic Control, Weight, and Blood Pressure in Patients with Type 2 Diabetes Attending a Specialist Endocrinology Practice in Canada: A Retrospective Cohort Analysis.
    Diabetes technology & therapeutics, 2017, Volume: 19, Issue:11

    Topics: Aged; Benzhydryl Compounds; Blood Glucose; Blood Pressure; Body Weight; Canada; Diabetes Mellitus, T

2017
Involvement of insulin resistance in D-galactose-induced age-related dementia in rats: Protective role of metformin and saxagliptin.
    PloS one, 2017, Volume: 12, Issue:8

    Topics: Adamantane; Aging; Animals; Biomarkers; Body Weight; Brain; Dementia; Dipeptides; Galactose; Glycate

2017
In utero and lactational exposure to metformin induces reproductive alterations in male rat offspring.
    Reproductive toxicology (Elmsford, N.Y.), 2017, Volume: 74

    Topics: Animals; Body Weight; Female; Fertility; Genitalia, Male; Hypoglycemic Agents; Lactation; Male; Mate

2017
In vivo therapeutic effect of combination treatment with metformin and Scutellaria baicalensis on maintaining bile acid homeostasis.
    PloS one, 2017, Volume: 12, Issue:9

    Topics: Algorithms; Animals; Bile Acids and Salts; Blood Glucose; Blotting, Western; Body Weight; Cholestero

2017
Cohort profile for the MASTERMIND study: using the Clinical Practice Research Datalink (CPRD) to investigate stratification of response to treatment in patients with type 2 diabetes.
    BMJ open, 2017, Oct-12, Volume: 7, Issue:10

    Topics: Adult; Aged; Body Mass Index; Body Weight; Databases as Topic; Diabetes Mellitus, Type 2; Disease Pr

2017
Modulation of the gut microbiota by metformin improves metabolic profiles in aged obese mice.
    Gut microbes, 2018, 03-04, Volume: 9, Issue:2

    Topics: Age Factors; Animals; Bacteria; Blood Glucose; Body Weight; Diet, High-Fat; Disease Models, Animal;

2018
The effects of metformin in type 1 diabetes mellitus.
    BMC endocrine disorders, 2018, Jan-16, Volume: 18, Issue:1

    Topics: Adult; Biomarkers; Blood Glucose; Body Weight; C-Peptide; Case-Control Studies; Diabetes Mellitus, T

2018
Comparison of costs and outcomes of dapagliflozin with other glucose-lowering therapy classes added to metformin using a short-term cost-effectiveness model in the US setting.
    Journal of medical economics, 2018, Volume: 21, Issue:5

    Topics: Benzhydryl Compounds; Blood Pressure; Body Weight; Cost-Benefit Analysis; Diabetes Mellitus, Type 2;

2018
IGF-1R and Leptin Expression Profile and the Effects of Metformin Treatment on Metabolic and Endocrine Parameters in PCOS Mice.
    BioMed research international, 2017, Volume: 2017

    Topics: Animals; Blood Glucose; Body Weight; Female; Gene Expression Regulation; Humans; Hypoglycemic Agents

2017
New insights on the modulatory roles of metformin or alpha-lipoic acid versus their combination in dextran sulfate sodium-induced chronic colitis in rats.
    Pharmacological reports : PR, 2018, Volume: 70, Issue:3

    Topics: Animals; Antioxidants; Body Weight; Colitis; Colon; Dextran Sulfate; Disease Models, Animal; Male; M

2018
Short-term combined treatment with exenatide and metformin is superior to glimepiride combined metformin in improvement of serum testosterone levels in type 2 diabetic patients with obesity.
    Andrologia, 2018, Volume: 50, Issue:7

    Topics: Adult; Anti-Obesity Agents; Blood Glucose; Body Weight; Diabetes Mellitus, Type 2; Drug Therapy, Com

2018
Metformin alleviates bleomycin-induced pulmonary fibrosis in rats: Pharmacological effects and molecular mechanisms.
    Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie, 2018, Volume: 97

    Topics: Animals; Biomarkers; Bleomycin; Body Weight; Bronchoalveolar Lavage Fluid; Cytokines; Disease Models

2018
Intrauterine exposure to metformin: Evaluation of endothelial and perivascular adipose tissue function in abdominal aorta of adult offspring.
    Life sciences, 2018, Aug-15, Volume: 207

    Topics: Adipose Tissue; Animals; Aorta, Abdominal; Body Weight; Dose-Response Relationship, Drug; Endothelia

2018
Efficacy and safety of replacing sitagliptin with canagliflozin in real-world patients with type 2 diabetes uncontrolled with sitagliptin combined with metformin and/or gliclazide: The SITA-CANA Switch Study.
    Diabetes & metabolism, 2018, Volume: 44, Issue:4

    Topics: Aged; Blood Glucose; Blood Pressure; Body Weight; Canagliflozin; Diabetes Mellitus, Type 2; Female;

2018
Aerobic exercise, but not metformin, prevents reduction of muscular performance by AMPk activation in mice on doxorubicin chemotherapy.
    Journal of cellular physiology, 2018, Volume: 233, Issue:12

    Topics: Adipose Tissue; AMP-Activated Protein Kinases; Animals; Autophagy; Body Weight; Doxorubicin; Enzyme

2018
Changes in HbA1c and weight, and treatment persistence, over the 18 months following initiation of second-line therapy in patients with type 2 diabetes: results from the United Kingdom Clinical Practice Research Datalink.
    BMC medicine, 2018, 07-16, Volume: 16, Issue:1

    Topics: Body Weight; Diabetes Mellitus, Type 2; Female; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Ma

2018
Synergistic action of ursolic acid and metformin in experimental model of insulin resistance and related behavioral alterations.
    European journal of pharmacology, 2018, Sep-15, Volume: 835

    Topics: Acetylcholinesterase; Adiponectin; Animals; Behavior, Animal; Blood Pressure; Body Weight; Brain; Co

2018
Sitagliptin attenuates myocardial apoptosis via activating LKB-1/AMPK/Akt pathway and suppressing the activity of GSK-3β and p38α/MAPK in a rat model of diabetic cardiomyopathy.
    Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie, 2018, Volume: 107

    Topics: AMP-Activated Protein Kinase Kinases; AMP-Activated Protein Kinases; Animals; Apoptosis; Biomarkers;

2018
Insulin Sensitizers Modulate GnRH Receptor Expression in PCOS Rats.
    Archives of medical research, 2018, Volume: 49, Issue:3

    Topics: Animals; Body Weight; Carboxymethylcellulose Sodium; Diet, High-Fat; Female; Glucose Tolerance Test;

2018
Antidiabetic Activity of Afobazole in Wistar Rats.
    Bulletin of experimental biology and medicine, 2018, Volume: 165, Issue:5

    Topics: Animals; Anti-Anxiety Agents; Benzimidazoles; Blood Glucose; Body Weight; Diabetes Mellitus, Experim

2018
Effects of the combination of metformin and exercise on glycated hemoglobin, functional capacity, lipid profile, quality of life, and body weight.
    The Journal of international medical research, 2019, Volume: 47, Issue:3

    Topics: Aged; Biomarkers; Blood Glucose; Body Weight; Case-Control Studies; Combined Modality Therapy; Diabe

2019
Long-term diabetes outcomes after bariatric surgery-managing medication withdrawl.
    International journal of obesity (2005), 2019, Volume: 43, Issue:11

    Topics: Adult; Bariatric Surgery; Body Weight; Diabetes Mellitus, Type 2; Female; Glycated Hemoglobin; Human

2019
Preventative effects of metformin on glucocorticoid-induced osteoporosis in rats.
    Journal of bone and mineral metabolism, 2019, Volume: 37, Issue:5

    Topics: Alendronate; Animals; Blood Glucose; Body Weight; Bone Density; Female; Femur; Glucocorticoids; Lipi

2019
Metformin prevents nephrolithiasis formation by inhibiting the expression of OPN and MCP-1 in vitro and in vivo.
    International journal of molecular medicine, 2019, Volume: 43, Issue:4

    Topics: Animals; Body Weight; Cell Death; Chemokine CCL2; Disease Models, Animal; Dogs; Ethylene Glycol; Hum

2019
Reply.
    Hepatology (Baltimore, Md.), 2019, Volume: 69, Issue:5

    Topics: Body Weight; Diabetes Mellitus, Type 2; Humans; Insulin Glargine; Lipids; Liraglutide; Metformin; No

2019
Letter to Editor: Role of Pharmacotherapy in Patients With Coexisting Nonalcoholic Fatty Liver Disease and Type 2 Diabetes Mellitus.
    Hepatology (Baltimore, Md.), 2019, Volume: 69, Issue:5

    Topics: Body Weight; Diabetes Mellitus, Type 2; Humans; Hypoglycemic Agents; Insulin Glargine; Lipids; Lirag

2019
Hepatoprotective effects of Cassia semen ethanol extract on non-alcoholic fatty liver disease in experimental rat.
    Pharmaceutical biology, 2019, Volume: 57, Issue:1

    Topics: Animals; Body Weight; Cassia; Liver; Male; Metformin; Non-alcoholic Fatty Liver Disease; Plant Extra

2019
Developmental and Full-Life Cycle Exposures to Guanylurea and Guanylurea-Metformin Mixtures Results in Adverse Effects on Japanese Medaka (Oryzias latipes).
    Environmental toxicology and chemistry, 2019, Volume: 38, Issue:5

    Topics: Animals; Body Weight; Female; Guanidines; Life Cycle Stages; Male; Metformin; Oryzias; Urea; Water P

2019
The evidence of metabolic-improving effect of metformin in Ay/a mice with genetically-induced melanocortin obesity and the contribution of hypothalamic mechanisms to this effect.
    PloS one, 2019, Volume: 14, Issue:3

    Topics: Agouti-Related Protein; Animals; Body Weight; Female; Gene Expression Regulation; Hypoglycemic Agent

2019
Metformin Attenuates Early-Stage Atherosclerosis in Mildly Hyperglycemic Oikawa-Nagao Mice.
    Journal of atherosclerosis and thrombosis, 2019, Dec-01, Volume: 26, Issue:12

    Topics: Animals; Atherosclerosis; Blood Glucose; Body Weight; Diabetes Mellitus, Type 2; Female; Hyperglycem

2019
Expert Opinion: Use of sodium glucose co-transporter type-2 inhibitors in South Asian population -The Pakistan perspective.
    JPMA. The Journal of the Pakistan Medical Association, 2019, Volume: 69, Issue:4

    Topics: Asia, Southeastern; Asia, Western; Asian People; Blood Pressure; Body Weight; Cholesterol; Cholester

2019
Incretin-Based Therapies for the Management of Nonalcoholic Fatty Liver Disease in Patients With Type 2 Diabetes.
    Hepatology (Baltimore, Md.), 2019, Volume: 69, Issue:6

    Topics: Body Weight; Diabetes Mellitus, Type 2; Humans; Incretins; Insulin Glargine; Lipids; Liraglutide; Me

2019
Maternal Metformin Treatment Improves Developmental and Metabolic Traits of IUGR Fetuses.
    Biomolecules, 2019, 04-29, Volume: 9, Issue:5

    Topics: Animals; Body Size; Body Weight; Female; Fetal Growth Retardation; Fetus; Metformin; Organ Size; Pre

2019
The combination of exercise training and sodium-glucose cotransporter-2 inhibition improves glucose tolerance and exercise capacity in a rodent model of type 2 diabetes.
    Metabolism: clinical and experimental, 2019, Volume: 97

    Topics: Animals; Blood Glucose; Body Weight; Diabetes Mellitus, Experimental; Diabetes Mellitus, Type 2; Dis

2019
Endoplasmic reticulum stress-induced iRhom2 up-regulation promotes macrophage-regulated cardiac inflammation and lipid deposition in high fat diet (HFD)-challenged mice: Intervention of fisetin and metformin.
    Free radical biology & medicine, 2019, Volume: 141

    Topics: Animals; Body Weight; Carrier Proteins; Diet, High-Fat; Echocardiography; Endoplasmic Reticulum Stre

2019
Lack of Durable Improvements in β-Cell Function Following Withdrawal of Pharmacological Interventions in Adults With Impaired Glucose Tolerance or Recently Diagnosed Type 2 Diabetes.
    Diabetes care, 2019, Volume: 42, Issue:9

    Topics: Adult; Arginine; B-Lymphocytes; Blood Glucose; Body Weight; C-Peptide; Diabetes Mellitus, Type 2; Fa

2019
Lack of Durable Improvements in β-Cell Function Following Withdrawal of Pharmacological Interventions in Adults With Impaired Glucose Tolerance or Recently Diagnosed Type 2 Diabetes.
    Diabetes care, 2019, Volume: 42, Issue:9

    Topics: Adult; Arginine; B-Lymphocytes; Blood Glucose; Body Weight; C-Peptide; Diabetes Mellitus, Type 2; Fa

2019
Lack of Durable Improvements in β-Cell Function Following Withdrawal of Pharmacological Interventions in Adults With Impaired Glucose Tolerance or Recently Diagnosed Type 2 Diabetes.
    Diabetes care, 2019, Volume: 42, Issue:9

    Topics: Adult; Arginine; B-Lymphocytes; Blood Glucose; Body Weight; C-Peptide; Diabetes Mellitus, Type 2; Fa

2019
Lack of Durable Improvements in β-Cell Function Following Withdrawal of Pharmacological Interventions in Adults With Impaired Glucose Tolerance or Recently Diagnosed Type 2 Diabetes.
    Diabetes care, 2019, Volume: 42, Issue:9

    Topics: Adult; Arginine; B-Lymphocytes; Blood Glucose; Body Weight; C-Peptide; Diabetes Mellitus, Type 2; Fa

2019
Ocimum kilimandscharicum L. restores ovarian functions in letrozole - induced Polycystic Ovary Syndrome (PCOS) in rats: Comparison with metformin.
    Life sciences, 2019, Sep-01, Volume: 232

    Topics: Aged; Animals; Antioxidants; Aromatase Inhibitors; Blood Glucose; Body Weight; Chromatography, High

2019
Evaluation of Kidney Function Parameters in Diabetic Rats Following Virgin Coconut Oil Diet.
    Folia medica, 2019, Jun-01, Volume: 61, Issue:2

    Topics: Animals; Blood Urea Nitrogen; Body Weight; Coconut Oil; Creatinine; Diabetes Mellitus, Experimental;

2019
Anti-diabetic effect of Murraya koenigii (L) and Olea europaea (L) leaf extracts on streptozotocin induced diabetic rats.
    Pakistan journal of pharmaceutical sciences, 2013, Volume: 26, Issue:2

    Topics: Administration, Oral; Animals; Biomarkers; Blood Glucose; Body Weight; Cholesterol; Creatinine; Diab

2013
Prenatal metformin exposure in mice programs the metabolic phenotype of the offspring during a high fat diet at adulthood.
    PloS one, 2013, Volume: 8, Issue:2

    Topics: Animals; Body Weight; Diet, High-Fat; Eating; Female; Fetus; Gene Expression Regulation; Glucose Tol

2013
Metformin inhibits the growth of human pancreatic cancer xenografts.
    Pancreas, 2013, Volume: 42, Issue:5

    Topics: Administration, Oral; Animals; Blotting, Western; Body Weight; Cell Line, Tumor; Dose-Response Relat

2013
Effect of metformin on the urinary metabolites of diet-induced-obese mice studied by ultra performance liquid chromatography coupled to time-of-flight mass spectrometry (UPLC-TOF/MS).
    Journal of chromatography. B, Analytical technologies in the biomedical and life sciences, 2013, Apr-15, Volume: 925

    Topics: Animals; Blood Glucose; Body Weight; Chromatography, High Pressure Liquid; Diet, High-Fat; Male; Mas

2013
Kidney function decline in metformin versus sulfonylurea initiators: assessment of time-dependent contribution of weight, blood pressure, and glycemic control.
    Pharmacoepidemiology and drug safety, 2013, Volume: 22, Issue:6

    Topics: Aged; Blood Glucose; Blood Pressure; Body Weight; Cohort Studies; Diabetes Mellitus, Type 2; Female;

2013
Hypoglycemic and anti-hyperglycemic study of Gynura procumbens leaf extracts.
    Asian Pacific journal of tropical biomedicine, 2013, Volume: 3, Issue:5

    Topics: Animals; Asteraceae; Blood Glucose; Body Weight; Diabetes Mellitus, Experimental; Flavonoids; Glucos

2013
Effect of the combination of metformin and fenofibrate on glucose homeostasis in diabetic Goto-Kakizaki rats.
    Experimental & molecular medicine, 2013, Jul-05, Volume: 45

    Topics: Animals; Blood Glucose; Body Weight; Diabetes Mellitus, Experimental; Drug Therapy, Combination; Exe

2013
The combined effect of metformin and L-cysteine on inflammation, oxidative stress and insulin resistance in streptozotocin-induced type 2 diabetes in rats.
    European journal of pharmacology, 2013, Aug-15, Volume: 714, Issue:1-3

    Topics: Animals; Body Weight; C-Reactive Protein; Caspase 3; Chemokine CCL2; Cysteine; Cytochromes c; Diabet

2013
Effect of kolaviron, a biflavonoid complex from Garcinia kola seeds, on the antioxidant, hormonal and spermatogenic indices of diabetic male rats.
    Andrologia, 2014, Volume: 46, Issue:8

    Topics: Animals; Blood Glucose; Body Weight; Diabetes Mellitus, Experimental; Drug Evaluation, Preclinical;

2014
Angiotensin II receptor blocker telmisartan prevents new-onset diabetes in pre-diabetes OLETF rats on a high-fat diet: evidence of anti-diabetes action.
    Canadian journal of diabetes, 2013, Volume: 37, Issue:3

    Topics: Angiotensin II Type 1 Receptor Blockers; Animals; Benzimidazoles; Benzoates; Blood Glucose; Blood Pr

2013
Metformin inhibits skin tumor promotion in overweight and obese mice.
    Cancer prevention research (Philadelphia, Pa.), 2014, Volume: 7, Issue:1

    Topics: Adenylate Kinase; Adiponectin; Animals; Body Weight; Carcinogenesis; Carcinoma, Squamous Cell; Diet;

2014
Changes in adiponectin level and fat distribution in patients with type 2 diabetes.
    European journal of clinical investigation, 2014, Volume: 44, Issue:2

    Topics: Adiponectin; Adipose Tissue; Aged; Blood Glucose; Body Fat Distribution; Body Weight; Diabetes Melli

2014
Efficacy and safety of insulin glargine added to a fixed-dose combination of metformin and a dipeptidyl peptidase-4 inhibitor: results of the GOLD observational study.
    Vascular health and risk management, 2013, Volume: 9

    Topics: Aged; Biomarkers; Blood Glucose; Body Weight; Diabetes Mellitus, Type 2; Dipeptidyl-Peptidase IV Inh

2013
[Оptimization of stable angina standard therapy in patients with concomitant osteoarthritis and obesity].
    Georgian medical news, 2013, Issue:224

    Topics: Adult; Aged; Angina, Stable; Anti-Inflammatory Agents, Non-Steroidal; Body Mass Index; Body Weight;

2013
[Effects of anti-diabetic therapy on overweight/obesity and dyslipidemia: traditional hypoglycemic agents (metformin, sulfonylureas, thiazolidinediones) versus glucagon-like peptide-1 analogs and dipeptidyl peptidase-4 inhibitors].
    Giornale italiano di cardiologia (2006), 2013, Volume: 14, Issue:12 Suppl

    Topics: Body Weight; Cardiovascular Diseases; Diabetes Mellitus, Type 2; Dipeptidyl-Peptidase IV Inhibitors;

2013
Characterization of the exocrine pancreas in the male Zucker diabetic fatty rat model of type 2 diabetes mellitus following 3 months of treatment with sitagliptin.
    Endocrinology, 2014, Volume: 155, Issue:3

    Topics: Administration, Oral; Animals; Blood Glucose; Body Weight; Cell Proliferation; Diabetes Mellitus, Ex

2014
Modeling effects of SGLT-2 inhibitor dapagliflozin treatment versus standard diabetes therapy on cardiovascular and microvascular outcomes.
    Diabetes, obesity & metabolism, 2014, Volume: 16, Issue:7

    Topics: Amputation, Surgical; Benzhydryl Compounds; Blood Glucose; Blood Pressure; Body Weight; Cardiovascul

2014
KDT501, a derivative from hops, normalizes glucose metabolism and body weight in rodent models of diabetes.
    PloS one, 2014, Volume: 9, Issue:1

    Topics: Adipocytes; Animals; Blood Glucose; Body Weight; Cells, Cultured; Diabetes Mellitus, Experimental; D

2014
Cardiovascular safety of combination therapies with incretin-based drugs and metformin compared with a combination of metformin and sulphonylurea in type 2 diabetes mellitus--a retrospective nationwide study.
    Diabetes, obesity & metabolism, 2014, Volume: 16, Issue:10

    Topics: Blood Glucose; Body Weight; Denmark; Diabetes Mellitus, Type 2; Dipeptidyl-Peptidase IV Inhibitors;

2014
Effect of vitamin D3 on behavioural and biochemical parameters in diabetes type 1-induced rats.
    Cell biochemistry and function, 2014, Volume: 32, Issue:6

    Topics: Acetylcholinesterase; Animals; Blood Glucose; Body Weight; Cerebral Cortex; Cholecalciferol; Diabete

2014
SGLT-2 inhibitors as second-line therapy in type 2 diabetes.
    The lancet. Diabetes & endocrinology, 2014, Volume: 2, Issue:9

    Topics: Benzhydryl Compounds; Blood Glucose; Blood Pressure; Body Weight; Diabetes Mellitus, Type 2; Drug Th

2014
Metformin impairs mitochondrial function in skeletal muscle of both lean and diabetic rats in a dose-dependent manner.
    PloS one, 2014, Volume: 9, Issue:6

    Topics: Animals; Body Weight; Diabetes Mellitus, Experimental; Diabetes Mellitus, Type 2; Humans; Insulin; M

2014
Comparison of the independent and combined effects of sub-chronic therapy with metformin and a stable GLP-1 receptor agonist on cognitive function, hippocampal synaptic plasticity and metabolic control in high-fat fed mice.
    Neuropharmacology, 2014, Volume: 86

    Topics: Animals; Anxiety; Body Weight; CA1 Region, Hippocampal; Cognition; Diet, High-Fat; Drug Therapy, Com

2014
Metformin suppresses lipid accumulation in skeletal muscle by promoting fatty acid oxidation.
    Clinical laboratory, 2014, Volume: 60, Issue:6

    Topics: Animals; Body Weight; Cell Line; Fatty Acids; Female; Lipid Metabolism; Male; Metformin; Mice; Mice,

2014
Antidiabetic effects of the Cimicifuga racemosa extract Ze 450 in vitro and in vivo in ob/ob mice.
    Phytomedicine : international journal of phytotherapy and phytopharmacology, 2014, Sep-25, Volume: 21, Issue:11

    Topics: AMP-Activated Protein Kinases; Animals; Benzophenanthridines; Berberine Alkaloids; Blood Glucose; Bo

2014
Effect of metformin on metabolic improvement and gut microbiota.
    Applied and environmental microbiology, 2014, Volume: 80, Issue:19

    Topics: Animals; Biomarkers; Blood Glucose; Body Weight; Clostridium; Diabetes Mellitus, Experimental; Diabe

2014
A follow-up of a randomised study of metformin and insulin in gestational diabetes mellitus: growth and development of the children at the age of 18 months.
    BJOG : an international journal of obstetrics and gynaecology, 2015, Volume: 122, Issue:7

    Topics: Adult; Body Height; Body Weight; Child Development; Diabetes, Gestational; Female; Follow-Up Studies

2015
Metformin reduces asymmetric dimethylarginine and prevents hypertension in spontaneously hypertensive rats.
    Translational research : the journal of laboratory and clinical medicine, 2014, Volume: 164, Issue:6

    Topics: Amidohydrolases; Animals; Arginine; Blood Pressure; Body Weight; Hypertension; Kidney; Lung; Male; M

2014
Hypoglycemic effect of catalpol on high-fat diet/streptozotocin-induced diabetic mice by increasing skeletal muscle mitochondrial biogenesis.
    Acta biochimica et biophysica Sinica, 2014, Volume: 46, Issue:9

    Topics: Animals; Base Sequence; Body Weight; Diet, High-Fat; DNA Primers; DNA, Mitochondrial; Glucose Tolera

2014
Metformin treatment improves weight and dyslipidemia in children with metabolic syndrome.
    Journal of pediatric endocrinology & metabolism : JPEM, 2015, Volume: 28, Issue:5-6

    Topics: Adolescent; Body Mass Index; Body Weight; Child; Dyslipidemias; Humans; Hypoglycemic Agents; Metabol

2015
Effect of metformin on sleep disorders in adolescent girls with polycystic ovarian syndrome.
    Journal of pediatric and adolescent gynecology, 2014, Volume: 27, Issue:6

    Topics: Adolescent; Blood Glucose; Body Mass Index; Body Weight; Child; Female; Hirsutism; Humans; Hypoglyce

2014
Protective effects of grape seed extract fractions with different degrees of polymerisation on blood glucose, lipids and hepatic oxidative stress in diabetic rats.
    Natural product research, 2015, Volume: 29, Issue:10

    Topics: Animals; Blood Glucose; Body Weight; Diabetes Mellitus, Experimental; Grape Seed Extract; Lipids; Li

2015
Economic implications of weight change in patients with type 2 diabetes mellitus.
    The American journal of managed care, 2014, Aug-01, Volume: 20, Issue:8

    Topics: Body Weight; Cost Savings; Diabetes Mellitus, Type 2; Female; Health Care Costs; Humans; Hypoglycemi

2014
Drug utilization, safety, and effectiveness of exenatide, sitagliptin, and vildagliptin for type 2 diabetes in the real world: data from the Italian AIFA Anti-diabetics Monitoring Registry.
    Nutrition, metabolism, and cardiovascular diseases : NMCD, 2014, Volume: 24, Issue:12

    Topics: Adamantane; Aged; Blood Glucose; Body Weight; Diabetes Mellitus, Type 2; Drug Utilization; Drug-Rela

2014
Is insulin the most effective injectable antihyperglycaemic therapy?
    Diabetes, obesity & metabolism, 2015, Volume: 17, Issue:2

    Topics: Blood Glucose; Body Weight; Diabetes Mellitus, Type 2; Exenatide; Fasting; Female; Glucagon-Like Pep

2015
What is the best approach to glycaemic control in patients with type 2 diabetes?
    Diabetes, obesity & metabolism, 2015, Volume: 17, Issue:2

    Topics: Blood Glucose; Body Weight; Diabetes Mellitus, Type 2; Female; Glycated Hemoglobin; Humans; Hypoglyc

2015
Observational and clinical trial findings on the comparative effectiveness of diabetes drugs showed agreement.
    Journal of clinical epidemiology, 2015, Volume: 68, Issue:2

    Topics: Body Weight; Diabetes Mellitus, Type 2; Female; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Me

2015
Sex differences in aging, life span and spontaneous tumorigenesis in 129/Sv mice neonatally exposed to metformin.
    Cell cycle (Georgetown, Tex.), 2015, Volume: 14, Issue:1

    Topics: Aging; Animals; Animals, Newborn; Body Temperature; Body Weight; Cell Transformation, Neoplastic; Es

2015
Metformin alleviates hepatosteatosis by restoring SIRT1-mediated autophagy induction via an AMP-activated protein kinase-independent pathway.
    Autophagy, 2015, Volume: 11, Issue:1

    Topics: AMP-Activated Protein Kinases; Animals; Autophagy; Blood Glucose; Body Weight; Caloric Restriction;

2015
Intracerebroventricular metformin decreases body weight but has pro-oxidant effects and decreases survival.
    Neurochemical research, 2015, Volume: 40, Issue:3

    Topics: Animals; Body Weight; Cells, Cultured; Hypoglycemia; Hypoglycemic Agents; Infusions, Intraventricula

2015
Should sulfonylureas remain an acceptable first-line add-on to metformin therapy in patients with type 2 diabetes? No, it's time to move on!
    Diabetes care, 2015, Volume: 38, Issue:1

    Topics: Blood Glucose; Body Weight; Diabetes Mellitus, Type 2; Feeding Behavior; Humans; Hyperglycemia; Hypo

2015
Prenatal metformin exposure in a maternal high fat diet mouse model alters the transcriptome and modifies the metabolic responses of the offspring.
    PloS one, 2014, Volume: 9, Issue:12

    Topics: Adipocytes; Adipokines; Adipose Tissue, White; Animals; Blood Glucose; Body Weight; Cell Size; Diet,

2014
Metformin and Rapamycin Reduce Pancreatic Cancer Growth in Obese Prediabetic Mice by Distinct MicroRNA-Regulated Mechanisms.
    Diabetes, 2015, Volume: 64, Issue:5

    Topics: Animals; Body Weight; Cell Cycle; Diet, Diabetic; Energy Intake; Glucose Intolerance; Hypoglycemic A

2015
Clinical effectiveness and safety of vildagliptin in >19 000 patients with type 2 diabetes: the GUARD study.
    Diabetes, obesity & metabolism, 2015, Volume: 17, Issue:6

    Topics: Adamantane; Adult; Aged; Blood Glucose; Body Mass Index; Body Weight; Diabetes Mellitus, Type 2; Dru

2015
Correlation between baseline characteristics and clinical outcomes in a large population of diabetes patients treated with liraglutide in a real-world setting in Italy.
    Clinical therapeutics, 2015, Mar-01, Volume: 37, Issue:3

    Topics: Aged; Blood Glucose; Body Mass Index; Body Weight; Diabetes Mellitus, Type 2; Female; Glycated Hemog

2015
Synergistic Effects of a GPR119 Agonist with Metformin on Weight Loss in Diet-Induced Obese Mice.
    The Journal of pharmacology and experimental therapeutics, 2015, Volume: 353, Issue:3

    Topics: Animals; Body Weight; Diet, High-Fat; Dose-Response Relationship, Drug; Drug Synergism; Eating; Gast

2015
Combination therapy with oleanolic acid and metformin as a synergistic treatment for diabetes.
    Journal of diabetes research, 2015, Volume: 2015

    Topics: Animals; Biomarkers; Body Weight; Diabetes Mellitus, Experimental; Diabetes Mellitus, Type 2; Diseas

2015
Add-On Treatment with Liraglutide Improves Glycemic Control in Patients with Type 2 Diabetes on Metformin Therapy.
    Diabetes technology & therapeutics, 2015, Volume: 17, Issue:7

    Topics: Aged; Blood Glucose; Blood Glucose Self-Monitoring; Blood Pressure; Body Weight; Diabetes Mellitus,

2015
The influence of age and metformin treatment status on reported gastrointestinal side effects with liraglutide treatment in type 2 diabetes.
    Diabetes research and clinical practice, 2015, Volume: 109, Issue:1

    Topics: Adult; Age Factors; Aged; Body Weight; Diabetes Mellitus, Type 2; Drug Therapy, Combination; Female;

2015
Alpha-lipoic acid reduces body weight and regulates triglycerides in obese patients with diabetes mellitus.
    Medicinski glasnik : official publication of the Medical Association of Zenica-Doboj Canton, Bosnia and Herzegovina, 2015, Volume: 12, Issue:2

    Topics: Body Weight; Cholesterol; Diabetes Mellitus, Type 2; Female; Humans; Male; Metformin; Middle Aged; O

2015
[THE EFFECTS OF LONG-TERM METFORMIN TREATMENT ON THE ACTIVITY OF ADENYLYL CYCLASE SYSTEM AND NO-SYNTHASES IN THE BRAIN AND THE MYOCARDIUM OF RATS WITH OBESITY].
    Tsitologiia, 2015, Volume: 57, Issue:5

    Topics: Adenylyl Cyclases; Adipose Tissue; Adrenergic Agonists; Animals; Body Weight; Brain; Cardiotonic Age

2015
Hyperandrogenism and Insulin Resistance, Not Changes in Body Weight, Mediate the Development of Endothelial Dysfunction in a Female Rat Model of Polycystic Ovary Syndrome (PCOS).
    Endocrinology, 2015, Volume: 156, Issue:11

    Topics: Androgen Antagonists; Androgens; Animals; Arteries; Blood Pressure; Body Weight; Dihydrotestosterone

2015
Use of Renally Inappropriate Medications in Older Veterans: A National Study.
    Journal of the American Geriatrics Society, 2015, Volume: 63, Issue:11

    Topics: Aged; Aged, 80 and over; Allopurinol; Aminohydrolases; Body Weight; Comorbidity; Cross-Sectional Stu

2015
Metformin for treatment of antipsychotic-induced weight gain in a South Asian population with schizophrenia or schizoaffective disorder: A double blind, randomized, placebo controlled study.
    Journal of psychopharmacology (Oxford, England), 2015, Volume: 29, Issue:12

    Topics: Adult; Antipsychotic Agents; Blood Glucose; Body Mass Index; Body Weight; Double-Blind Method; Femal

2015
Metformin inhibits early stage diethylnitrosamine‑induced hepatocarcinogenesis in rats.
    Molecular medicine reports, 2016, Volume: 13, Issue:1

    Topics: Adenylate Kinase; Animals; Blotting, Western; Body Weight; Carcinogenesis; Carcinoma, Hepatocellular

2016
Does metformin improve in vitro maturation and ultrastructure of oocytes retrieved from estradiol valerate polycystic ovary syndrome-induced rats.
    Journal of ovarian research, 2015, Nov-14, Volume: 8

    Topics: Animals; Blood Glucose; Body Weight; Contraceptive Agents; Cumulus Cells; Disease Models, Animal; Es

2015
The effect of metformin on neuronal activity in the appetite-regulating brain regions of mice fed a high-fat diet during an anorectic period.
    Physiology & behavior, 2016, Feb-01, Volume: 154

    Topics: Analysis of Variance; Animals; Anorexia; Body Weight; Brain; Diet, High-Fat; Eating; Gene Expression

2016
Cardioprotective effect of metformin in lipopolysaccharide-induced sepsis via suppression of toll-like receptor 4 (TLR4) in heart.
    European journal of pharmacology, 2016, Feb-05, Volume: 772

    Topics: AMP-Activated Protein Kinases; Animals; Body Weight; Cardiotonic Agents; Gene Expression Regulation;

2016
Determinants of Glycemic Response to Add-On Therapy with a Dipeptidyl Peptidase-4 Inhibitor: A Retrospective Cohort Study Using a United Kingdom Primary Care Database.
    Diabetes technology & therapeutics, 2016, Volume: 18, Issue:2

    Topics: Aged; Blood Glucose; Body Weight; Databases, Factual; Diabetes Mellitus, Type 2; Dipeptidyl-Peptidas

2016
[Metformin and changes in blood pressure and heart rate in lean patients with polycystic ovary syndrome (PCOS)--preliminary study].
    Przeglad lekarski, 2015, Volume: 72, Issue:6

    Topics: Adolescent; Blood Pressure; Body Weight; Female; Heart Rate; Humans; Hypoglycemic Agents; Metformin;

2015
Effects of Exenatide on Metabolic Changes, Sexual Hormones, Inflammatory Cytokines, Adipokines, and Weight Change in a DHEA-Treated Rat Model.
    Reproductive sciences (Thousand Oaks, Calif.), 2016, Volume: 23, Issue:9

    Topics: Adipokines; Animals; Body Weight; Cytokines; Dehydroepiandrosterone; Disease Models, Animal; Exenati

2016
Important differences in the durability of glycaemic response among second-line treatment options when added to metformin in type 2 diabetes: a retrospective cohort study.
    Annals of medicine, 2016, Volume: 48, Issue:4

    Topics: Aged; Blood Glucose; Body Weight; Cohort Studies; Diabetes Mellitus, Type 2; Dipeptidyl-Peptidase IV

2016
Effects of canagliflozin on body weight and body composition in patients with type 2 diabetes over 104 weeks.
    Postgraduate medicine, 2016, Volume: 128, Issue:4

    Topics: Adiposity; Aged; Body Composition; Body Mass Index; Body Weight; Canagliflozin; Clinical Trials, Pha

2016
Effects of canagliflozin on body weight and body composition in patients with type 2 diabetes over 104 weeks.
    Postgraduate medicine, 2016, Volume: 128, Issue:4

    Topics: Adiposity; Aged; Body Composition; Body Mass Index; Body Weight; Canagliflozin; Clinical Trials, Pha

2016
Effects of canagliflozin on body weight and body composition in patients with type 2 diabetes over 104 weeks.
    Postgraduate medicine, 2016, Volume: 128, Issue:4

    Topics: Adiposity; Aged; Body Composition; Body Mass Index; Body Weight; Canagliflozin; Clinical Trials, Pha

2016
Effects of canagliflozin on body weight and body composition in patients with type 2 diabetes over 104 weeks.
    Postgraduate medicine, 2016, Volume: 128, Issue:4

    Topics: Adiposity; Aged; Body Composition; Body Mass Index; Body Weight; Canagliflozin; Clinical Trials, Pha

2016
Metformin Prevents Fatty Liver and Improves Balance of White/Brown Adipose in an Obesity Mouse Model by Inducing FGF21.
    Mediators of inflammation, 2016, Volume: 2016

    Topics: 3T3-L1 Cells; Adipose Tissue; Adiposity; Animals; Body Weight; CD4-Positive T-Lymphocytes; Diet, Hig

2016
Association Between Weight Change, Clinical Outcomes, and Health Care Costs in Patients with Type 2 Diabetes.
    Journal of managed care & specialty pharmacy, 2016, Volume: 22, Issue:5

    Topics: Blood Pressure; Body Weight; Cardiovascular Diseases; Cholesterol, LDL; Cohort Studies; Diabetes Mel

2016
Effect of Vanadyl Rosiglitazone, a New Insulin-Mimetic Vanadium Complexes, on Glucose Homeostasis of Diabetic Mice.
    Applied biochemistry and biotechnology, 2016, Volume: 180, Issue:5

    Topics: Animals; Blood Glucose; Body Weight; Diabetes Mellitus, Experimental; Disease Models, Animal; Drinki

2016
Addition of sulphonylurea to metformin does not relevantly change body weight: a prospective observational cohort study (ZODIAC-39).
    Diabetes, obesity & metabolism, 2016, Volume: 18, Issue:10

    Topics: Aged; Blood Glucose; Body Weight; Diabetes Mellitus, Type 2; Drug Therapy, Combination; Female; Glyc

2016
Changes in Levels of Biomarkers Associated with Adipocyte Function and Insulin and Glucagon Kinetics During Treatment with Dapagliflozin Among Obese Type 2 Diabetes Mellitus Patients.
    Drugs in R&D, 2016, Volume: 16, Issue:3

    Topics: Adipocytes; Adiponectin; Adult; Benzhydryl Compounds; Biomarkers; Blood Glucose; Body Weight; C-Reac

2016
Additional effect of metformin and celecoxib against lipid dysregulation and adipose tissue inflammation in high-fat fed rats with insulin resistance and fatty liver.
    European journal of pharmacology, 2016, Oct-15, Volume: 789

    Topics: Adipocytes; Adipokines; Adipose Tissue; AMP-Activated Protein Kinases; Animals; Blood Pressure; Body

2016
The paraoxonase 1 (PON1), platelet-activating factor acetylohydrolase (PAF-AH) and dimethylarginine dimethylaminohydrolase (DDAH) activity in the metformin treated normal and diabetic rats.
    European journal of pharmacology, 2016, Oct-15, Volume: 789

    Topics: 1-Alkyl-2-acetylglycerophosphocholine Esterase; Amidohydrolases; Animals; Aryldialkylphosphatase; Bo

2016
Metformin ameliorates obesity-associated hypertriglyceridemia in mice partly through the apolipoprotein A5 pathway.
    Biochemical and biophysical research communications, 2016, 09-23, Volume: 478, Issue:3

    Topics: Animals; Apolipoprotein A-V; Body Weight; Hep G2 Cells; Humans; Hypertriglyceridemia; Male; Metformi

2016
Antidiabetic effects of Cuscuta reflexa Roxb. in streptozotocin induced diabetic rats.
    Journal of ethnopharmacology, 2016, Nov-04, Volume: 192

    Topics: Animals; Biomarkers; Blood Glucose; Body Weight; Cuscuta; Diabetes Mellitus, Experimental; Dose-Resp

2016
Accumulation of methylglyoxal and d-lactate in Pb-induced nephrotoxicity in rats.
    Biomedical chromatography : BMC, 2017, Volume: 31, Issue:5

    Topics: Animals; Biomarkers; Body Weight; Creatinine; Kidney; Kidney Diseases; L-Lactate Dehydrogenase; Lact

2017
Pleiotropic protective effects of Vitamin D against high fat diet-induced metabolic syndrome in rats: One for all.
    European journal of pharmacology, 2016, Dec-05, Volume: 792

    Topics: Animals; Biomarkers; Body Weight; Calcium; Cytoprotection; Diet, High-Fat; Drug Interactions; Hypert

2016
Metformin Reduces Lipogenesis Markers in Obese Mice Fed a Low-Carbohydrate and High-Fat Diet.
    Lipids, 2016, Volume: 51, Issue:12

    Topics: Acetyl-CoA Carboxylase; Adipose Tissue; Administration, Oral; Animals; Biomarkers; Body Weight; Diet

2016
Metformin preconditioned adipose derived mesenchymal stem cells is a better option for the reversal of diabetes upon transplantation.
    Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie, 2016, Volume: 84

    Topics: Adipose Tissue; Animals; Blood Glucose; Body Weight; Cytokines; Diabetes Mellitus, Type 2; Diet, Hig

2016
Lean Body Weight and Metformin Are Insufficient to Prevent Endometrial Hyperplasia in Mice Harboring Inactivating Mutations in PTEN.
    Oncology, 2017, Volume: 92, Issue:2

    Topics: Adiponectin; Animals; Body Weight; Endometrial Hyperplasia; Female; Hypoglycemic Agents; Metformin;

2017
Predictors of menstruation restoration during metformin administration for treatment of antipsychotic drug-induced amenorrhea: A post hoc analysis.
    Schizophrenia research, 2017, Volume: 190

    Topics: Amenorrhea; Antipsychotic Agents; Body Weight; Female; Follicle Stimulating Hormone; Humans; Hypogly

2017
Adiponectin receptors: expression in Zucker diabetic rats and effects of fenofibrate and metformin.
    Metabolism: clinical and experimental, 2008, Volume: 57, Issue:7

    Topics: Animals; Blood Glucose; Body Weight; Diabetes Mellitus, Experimental; Eating; Fatty Acids, Nonesteri

2008
Strategies to control antipsychotic-induced weight gain.
    Psychoneuroendocrinology, 2008, Volume: 33, Issue:8

    Topics: Anti-Obesity Agents; Antipsychotic Agents; Awareness; Body Weight; Bupropion; Clinical Competence; F

2008
Metformin protects the brain against the oxidative imbalance promoted by type 2 diabetes.
    Medicinal chemistry (Shariqah (United Arab Emirates)), 2008, Volume: 4, Issue:4

    Topics: Animals; Blood Glucose; Body Weight; Brain; Diabetes Mellitus, Type 2; Glutathione; Hydrogen Peroxid

2008
Effect of FeSO4 treatment on glucose metabolism in diabetic rats.
    Biometals : an international journal on the role of metal ions in biology, biochemistry, and medicine, 2008, Volume: 21, Issue:6

    Topics: Animals; Blood Glucose; Body Weight; Citric Acid Cycle; Diabetes Mellitus, Experimental; Electron Tr

2008
No effect of metformin on the innate airway hyperresponsiveness and increased responses to ozone observed in obese mice.
    Journal of applied physiology (Bethesda, Md. : 1985), 2008, Volume: 105, Issue:4

    Topics: Administration, Oral; Animals; Asthma; Blood Glucose; Body Weight; Bronchial Hyperreactivity; Bronch

2008
Metformin slows down aging and extends life span of female SHR mice.
    Cell cycle (Georgetown, Tex.), 2008, Sep-01, Volume: 7, Issue:17

    Topics: Aging; Animals; Body Temperature; Body Weight; Drinking Behavior; Estrous Cycle; Feeding Behavior; F

2008
Nigella sativa inhibits intestinal glucose absorption and improves glucose tolerance in rats.
    Journal of ethnopharmacology, 2009, Jan-30, Volume: 121, Issue:3

    Topics: Animals; Body Weight; Dose-Response Relationship, Drug; Female; Glucose; Glucose Tolerance Test; Hyp

2009
Effects of basal insulin analog and metformin on glycaemia control and weight as risk factors for endothelial dysfunction.
    Bosnian journal of basic medical sciences, 2008, Volume: 8, Issue:4

    Topics: Blood Glucose; Body Weight; Cardiovascular Diseases; Diabetes Mellitus, Type 2; Endothelium, Vascula

2008
Comparative therapeutic effects of metformin and vitamin E in a model of non-alcoholic steatohepatitis in the young rat.
    European journal of pharmacology, 2009, Feb-14, Volume: 604, Issue:1-3

    Topics: Animals; Antioxidants; Blotting, Western; Body Weight; Disease Models, Animal; Fatty Liver; Lipid Pe

2009
Effect of chronic co-administration of metformin and vitamin C on plasma glucose and lipid concentrations in normal rats.
    African journal of medicine and medical sciences, 2007, Volume: 36, Issue:2

    Topics: Administration, Oral; Animals; Ascorbic Acid; Blood Glucose; Body Weight; Drug Therapy, Combination;

2007
db/+ Mice as an alternate model in antidiabetic drug discovery research.
    Archives of medical research, 2009, Volume: 40, Issue:2

    Topics: Animals; Body Weight; Diabetes Mellitus, Experimental; Disease Models, Animal; Drug Discovery; Gluco

2009
[Metformin also as first choice in patients with normal weight. Has its use increased?].
    Atencion primaria, 2009, Volume: 41, Issue:6

    Topics: Body Weight; Diabetes Mellitus, Type 2; Humans; Hypoglycemic Agents; Longitudinal Studies; Metformin

2009
Nonalcoholic hepatic steatosis in Zucker diabetic rats: spontaneous evolution and effects of metformin and fenofibrate.
    Obesity (Silver Spring, Md.), 2009, Volume: 17, Issue:7

    Topics: Animals; Blood Glucose; Body Weight; Diabetes Mellitus, Experimental; Disease Models, Animal; Eating

2009
Androgen receptor antagonism and an insulin sensitizer block the advancement of vaginal opening by high-fat diet in mice.
    Biology of reproduction, 2009, Volume: 81, Issue:6

    Topics: Analysis of Variance; Androgen Antagonists; Animals; Body Weight; Diet, Fat-Restricted; Dietary Fats

2009
Total and acylated ghrelin levels in type 2 diabetic patients: similar levels observed after treatment with metformin, pioglitazone or diet therapy.
    Experimental and clinical endocrinology & diabetes : official journal, German Society of Endocrinology [and] German Diabetes Association, 2009, Volume: 117, Issue:8

    Topics: Acylation; Blood Glucose; Body Mass Index; Body Weight; Diabetes Mellitus, Type 2; Female; Ghrelin;

2009
Pregnancy outcomes in women with gestational diabetes treated with metformin or insulin: a case-control study.
    Diabetic medicine : a journal of the British Diabetic Association, 2009, Volume: 26, Issue:8

    Topics: Birth Weight; Blood Glucose; Body Weight; Case-Control Studies; Diabetes, Gestational; Female; Human

2009
Conjugated linoleic acid activates AMP-activated protein kinase and reduces adiposity more effectively when used with metformin in mice.
    The Journal of nutrition, 2009, Volume: 139, Issue:12

    Topics: 3T3 Cells; Adipocytes; AMP-Activated Protein Kinases; Animals; Body Weight; Cell Culture Techniques;

2009
Lipase maturation factor 1: its expression in Zucker diabetic rats, and effects of metformin and fenofibrate.
    Diabetes & metabolism, 2009, Volume: 35, Issue:6

    Topics: Adipose Tissue; Analysis of Variance; Animals; Blood Glucose; Body Weight; Diabetes Mellitus; Enzyme

2009
Toxicity and toxicokinetics of metformin in rats.
    Toxicology and applied pharmacology, 2010, Mar-15, Volume: 243, Issue:3

    Topics: Animals; Area Under Curve; Blood Cell Count; Blood Chemical Analysis; Body Weight; Chromatography, H

2010
Treatment with sitagliptin or metformin does not increase body weight despite predicted reductions in urinary glucose excretion.
    Journal of diabetes science and technology, 2009, Volume: 3, Issue:1

    Topics: Body Weight; Diabetes Mellitus, Type 2; Glucose; Humans; Hypoglycemic Agents; Metformin; Models, The

2009
Metformin normalizes type 2 diabetes-induced decrease in cell proliferation and neuroblast differentiation in the rat dentate gyrus.
    Neurochemical research, 2010, Volume: 35, Issue:4

    Topics: Animals; Blood Glucose; Body Weight; Cell Proliferation; Dentate Gyrus; Diabetes Mellitus, Experimen

2010
Effects of metformin on serum levels of sex hormone, leptin and insulin in ovariectomized Sprague-Dawley rats.
    Die Pharmazie, 2009, Volume: 64, Issue:12

    Topics: Animals; Body Weight; Estradiol; Female; Gonadal Steroid Hormones; Hypoglycemic Agents; Insulin; Lep

2009
The anorexigenic effects of metformin involve increases in hypothalamic leptin receptor expression.
    Metabolism: clinical and experimental, 2011, Volume: 60, Issue:3

    Topics: Agouti-Related Protein; Animals; Blood Glucose; Body Weight; Eating; Humans; Hypoglycemic Agents; Hy

2011
Metformin supplementation and life span in Fischer-344 rats.
    The journals of gerontology. Series A, Biological sciences and medical sciences, 2010, Volume: 65, Issue:5

    Topics: Animals; Blood Glucose; Body Temperature; Body Weight; Eating; Food Additives; Hypoglycemic Agents;

2010
Understanding the inter-relationship between improved glycaemic control, hypoglycaemia and weight change within a long-term economic model.
    Diabetes, obesity & metabolism, 2010, Volume: 12, Issue:5

    Topics: Blood Glucose; Body Weight; Cost-Benefit Analysis; Diabetes Mellitus, Type 2; Humans; Hypoglycemia;

2010
Metformin reduces body weight gain and improves glucose intolerance in high-fat diet-fed C57BL/6J mice.
    Biological & pharmaceutical bulletin, 2010, Volume: 33, Issue:6

    Topics: Animals; Blood Glucose; Body Weight; Dietary Fats; Energy Intake; Glucagon-Like Peptide 1; Glucose I

2010
Hyperinsulinemia precedes insulin resistance in mice lacking pancreatic beta-cell leptin signaling.
    Endocrinology, 2010, Volume: 151, Issue:9

    Topics: Adiposity; Animals; Blood Glucose; Body Weight; Diazoxide; Eating; Female; Hyperinsulinism; Hypoglyc

2010
Effects of metformin on rosiglitazone-induced cardiac hypertrophy in mice.
    Biological & pharmaceutical bulletin, 2010, Volume: 33, Issue:9

    Topics: Animals; Body Weight; Cardiomegaly; Drug Therapy, Combination; Eating; Male; Metformin; Mice; Mice,

2010
Countering side effects.
    Journal of psychiatric practice, 2010, Volume: 16, Issue:5

    Topics: Antipsychotic Agents; Body Weight; Humans; Hypoglycemic Agents; Metabolic Syndrome; Metformin; Psych

2010
Glycemic and weight changes after persistent use of incident oral diabetes therapy: a Veterans Administration retrospective cohort study.
    Pharmacoepidemiology and drug safety, 2010, Volume: 19, Issue:11

    Topics: Administration, Oral; Aged; Blood Glucose; Body Mass Index; Body Weight; Cohort Studies; Diabetes Me

2010
[Effect of metformin on the formation of hepatic fibrosis in type 2 diabetic rats].
    Yao xue xue bao = Acta pharmaceutica Sinica, 2010, Volume: 45, Issue:6

    Topics: Actins; Animals; Apoptosis; Blood Glucose; Body Weight; Diabetes Mellitus, Experimental; Diabetes Me

2010
Effect of combining rosiglitazone with either metformin or insulin on β-cell mass and function in an animal model of Type 2 diabetes characterized by reduced β-cell mass at birth.
    Journal of diabetes, 2011, Volume: 3, Issue:1

    Topics: Adiposity; Analysis of Variance; Animals; Animals, Newborn; Blood Glucose; Body Weight; Diabetes Mel

2011
Pronounced weight gain in insulin-treated patients with type 2 diabetes mellitus is associated with an unfavourable cardiometabolic risk profile.
    The Netherlands journal of medicine, 2010, Volume: 68, Issue:11

    Topics: Aged; Body Fat Distribution; Body Weight; Cardiovascular Diseases; Cross-Sectional Studies; Diabetes

2010
Summaries for patients: Does adding exenatide to insulin treatment benefit patients with type 2 diabetes?
    Annals of internal medicine, 2011, Jan-18, Volume: 154, Issue:2

    Topics: Aged; Body Weight; Diabetes Mellitus, Type 2; Drug Administration Schedule; Drug Therapy, Combinatio

2011
Gender differences in metformin effect on aging, life span and spontaneous tumorigenesis in 129/Sv mice.
    Aging, 2010, Volume: 2, Issue:12

    Topics: Age Factors; Aging; Animals; Blood Glucose; Body Temperature; Body Weight; Cholesterol; Chromosome A

2010
Insulin and metformin may prevent renal injury in young type 2 diabetic Goto-Kakizaki rats.
    European journal of pharmacology, 2011, Feb-25, Volume: 653, Issue:1-3

    Topics: Animals; Blood Glucose; Body Weight; Diabetes Mellitus, Experimental; Diabetes Mellitus, Type 2; Dia

2011
Metformin and atorvastatin combination further protect the liver in type 2 diabetes with hyperlipidaemia.
    Diabetes/metabolism research and reviews, 2011, Volume: 27, Issue:1

    Topics: Animals; Anticholesteremic Agents; Atorvastatin; Body Weight; C-Reactive Protein; Diabetes Complicat

2011
Protection of cholinergic and antioxidant system contributes to the effect of berberine ameliorating memory dysfunction in rat model of streptozotocin-induced diabetes.
    Behavioural brain research, 2011, Jun-20, Volume: 220, Issue:1

    Topics: Acetylcholine; Administration, Oral; Analysis of Variance; Animals; Antioxidants; Ascorbic Acid; Ber

2011
Effect of metformin therapy on cardiac function and survival in a volume-overload model of heart failure in rats.
    Clinical science (London, England : 1979), 2011, Volume: 121, Issue:1

    Topics: AMP-Activated Protein Kinase Kinases; Animals; Blood Glucose; Body Weight; Disease Models, Animal; D

2011
Management of cardiovascular risk factors with pioglitazone combination therapies in type 2 diabetes: an observational cohort study.
    Cardiovascular diabetology, 2011, Feb-11, Volume: 10

    Topics: Aged; Biomarkers; Blood Glucose; Blood Pressure; Body Mass Index; Body Weight; Cardiovascular Diseas

2011
Anti-diabetic effects of mildronate alone or in combination with metformin in obese Zucker rats.
    European journal of pharmacology, 2011, May-11, Volume: 658, Issue:2-3

    Topics: Animals; Blood Glucose; Body Weight; Cell Nucleus; Drug Combinations; Eating; Gene Expression Regula

2011
If started early in life, metformin treatment increases life span and postpones tumors in female SHR mice.
    Aging, 2011, Volume: 3, Issue:2

    Topics: Age Factors; Animals; Body Temperature; Body Weight; Drinking; Eating; Estrous Cycle; Female; Humans

2011
Glibenclamide or metformin combined with honey improves glycemic control in streptozotocin-induced diabetic rats.
    International journal of biological sciences, 2011, Mar-14, Volume: 7, Issue:2

    Topics: Animals; Bilirubin; Blood Glucose; Body Weight; Creatinine; Diabetes Mellitus, Experimental; Eating;

2011
Investigation of the potential effects of metformin on atherothrombotic risk factors in hyperlipidemic rats.
    European journal of pharmacology, 2011, Jun-01, Volume: 659, Issue:2-3

    Topics: Animals; Antioxidants; Aorta; Atherosclerosis; Blood Coagulation; Body Weight; Carotid Arteries; Cho

2011
The effect of metformin on the myocardial tolerance to ischemia-reperfusion injury in the rat model of diabetes mellitus type II.
    Experimental diabetes research, 2011, Volume: 2011

    Topics: Animals; Animals, Newborn; Blood Glucose; Body Weight; Diabetes Mellitus, Experimental; Disease Mode

2011
Reduced cell proliferation and neuroblast differentiation in the dentate gyrus of high fat diet-fed mice are ameliorated by metformin and glimepiride treatment.
    Neurochemical research, 2011, Volume: 36, Issue:12

    Topics: Animals; Body Weight; Brain-Derived Neurotrophic Factor; Cell Differentiation; Cell Proliferation; D

2011
Metformin treatment has no beneficial effect in a dose-response survival study in the SOD1(G93A) mouse model of ALS and is harmful in female mice.
    PloS one, 2011, Volume: 6, Issue:9

    Topics: Aging; Amino Acid Substitution; Amyotrophic Lateral Sclerosis; Animals; Body Weight; Cell Count; Dis

2011
Hypoglycaemic activity and molecular mechanisms of Caesalpinia ferrea Martius bark extract on streptozotocin-induced diabetes in Wistar rats.
    Journal of ethnopharmacology, 2011, Oct-11, Volume: 137, Issue:3

    Topics: Acetyl-CoA Carboxylase; Administration, Oral; AMP-Activated Protein Kinases; Animals; Blood Glucose;

2011
Insulin sensitizers may attenuate lean mass loss in older men with diabetes.
    Diabetes care, 2011, Volume: 34, Issue:11

    Topics: Absorptiometry, Photon; Adipose Tissue; Aged; Aged, 80 and over; Aging; Blood Glucose; Body Composit

2011
Metformin regulates hepatic lipid metabolism through activating AMP-activated protein kinase and inducing ATGL in laying hens.
    European journal of pharmacology, 2011, Dec-05, Volume: 671, Issue:1-3

    Topics: Abdominal Fat; AMP-Activated Protein Kinases; Animals; Body Weight; Chickens; Eating; Enzyme Activat

2011
Drug treatment of obesity.
    The Psychiatric clinics of North America, 2011, Volume: 34, Issue:4

    Topics: Adolescent; Adult; Anti-Obesity Agents; Antidepressive Agents, Second-Generation; Body Weight; Bupro

2011
Improvement of metabolic parameters and vascular function by metformin in obese non-diabetic rats.
    Life sciences, 2012, Jan-30, Volume: 90, Issue:5-6

    Topics: Acetylcholine; Animals; Blood Pressure; Body Weight; Disease Models, Animal; Dyslipidemias; Epoprost

2012
Population pharmacokinetics of metformin in obese and non-obese patients with type 2 diabetes mellitus.
    European journal of clinical pharmacology, 2012, Volume: 68, Issue:6

    Topics: Adult; Aged; Aged, 80 and over; Body Weight; Diabetes Mellitus, Type 2; Female; Humans; Hypoglycemic

2012
Anti-diabetic activities of Acanthopanax senticosus polysaccharide (ASP) in combination with metformin.
    International journal of biological macromolecules, 2012, Apr-01, Volume: 50, Issue:3

    Topics: Animals; Bilirubin; Blood Glucose; Body Weight; Creatinine; Diabetes Mellitus, Experimental; Drug In

2012
Therapeutic trial of metformin and bortezomib in a mouse model of tuberous sclerosis complex (TSC).
    PloS one, 2012, Volume: 7, Issue:2

    Topics: Animals; Body Weight; Boronic Acids; Bortezomib; Disease Models, Animal; Humans; Immunoblotting; Imm

2012
Downregulation of chemerin and alleviation of endoplasmic reticulum stress by metformin in adipose tissue of rats.
    Diabetes research and clinical practice, 2012, Volume: 97, Issue:2

    Topics: Adipokines; Adipose Tissue; Animals; Blood Glucose; Body Weight; Chemokines; Diet, High-Fat; Down-Re

2012
Cardioprotective effects of metformin and vildagliptin in adult rats with insulin resistance induced by a high-fat diet.
    Endocrinology, 2012, Volume: 153, Issue:8

    Topics: Adamantane; Animals; Blood Glucose; Body Weight; Diet, High-Fat; Dipeptidyl-Peptidase IV Inhibitors;

2012
Attenuation of insulin resistance, metabolic syndrome and hepatic oxidative stress by resveratrol in fructose-fed rats.
    Pharmacological research, 2012, Volume: 66, Issue:3

    Topics: Animals; Ascorbic Acid; Blood Glucose; Body Weight; Catalase; Eating; Fructose; Glucose Tolerance Te

2012
A high-fat-diet-induced cognitive deficit in rats that is not prevented by improving insulin sensitivity with metformin.
    Diabetologia, 2012, Volume: 55, Issue:11

    Topics: Alzheimer Disease; Animals; Behavior, Animal; Body Weight; Brain; Cognition Disorders; Conditioning,

2012
[Pharmacogenetic features of the effect of metformin in patients with coronary heart disease in the presence of metabolic syndrome and type 2 diabetes mellitus in terms of PPAR-gamma2 gene polymorphism].
    Terapevticheskii arkhiv, 2012, Volume: 84, Issue:9

    Topics: Aged; Alleles; Body Weight; Case-Control Studies; Coronary Disease; Cytokines; Diabetes Mellitus, Ty

2012
Gemfibrozil and its combination with metformin on pleiotropic effect on IL-10 and adiponectin and anti-atherogenic treatment in insulin resistant type 2 diabetes mellitus rats.
    Inflammopharmacology, 2013, Volume: 21, Issue:2

    Topics: Adiponectin; Animals; Body Weight; Diabetes Mellitus, Experimental; Diabetes Mellitus, Type 2; Drug

2013
Role of PKC and CaV1.2 in detrusor overactivity in a model of obesity associated with insulin resistance in mice.
    PloS one, 2012, Volume: 7, Issue:11

    Topics: Adiposity; Amlodipine; Animals; Body Weight; Calcium Channel Blockers; Calcium Channels, L-Type; Cal

2012
Renal uptake of substrates for organic anion transporters Oat1 and Oat3 and organic cation transporters Oct1 and Oct2 is altered in rats with adenine-induced chronic renal failure.
    Journal of pharmaceutical sciences, 2013, Volume: 102, Issue:3

    Topics: Adenine; Animals; Anti-Bacterial Agents; Body Weight; Gene Expression; Hypoglycemic Agents; Kidney;

2013
Metformin temporal and localized effects on gut glucose metabolism assessed using 18F-FDG PET in mice.
    Journal of nuclear medicine : official publication, Society of Nuclear Medicine, 2013, Volume: 54, Issue:2

    Topics: Animals; Blood Glucose; Body Weight; Carrier Proteins; Female; Fluorodeoxyglucose F18; Gastrointesti

2013
Nateglinide in combination with metformin in Chinese patients with type 2 diabetes mellitus: a post-marketing surveillance study.
    Clinical drug investigation, 2013, Volume: 33, Issue:3

    Topics: Aged; Body Weight; Cyclohexanes; Diabetes Mellitus, Type 2; Female; Humans; Hypoglycemic Agents; Mal

2013
Metformin decreases meal size and number and increases c-Fos expression in the nucleus tractus solitarius of obese mice.
    Physiology & behavior, 2013, Feb-17, Volume: 110-111

    Topics: Animals; Avoidance Learning; Body Weight; Circadian Rhythm; Dietary Fats; Eating; Energy Intake; Ene

2013
Durability of efficacy and long-term safety profile of glyburide/metformin tablets in patients with type 2 diabetes mellitus: an open-label extension study.
    Clinical therapeutics, 2002, Volume: 24, Issue:9

    Topics: Blood Glucose; Body Weight; Diabetes Mellitus, Type 2; Dose-Response Relationship, Drug; Drug Therap

2002
Therapeutic approach in insulin resistance with acanthosis nigricans.
    International journal of clinical practice, 2002, Volume: 56, Issue:8

    Topics: Acanthosis Nigricans; Adolescent; Adult; Body Mass Index; Body Weight; Diabetes Complications; Diabe

2002
Transfer of metformin into human milk.
    Diabetologia, 2002, Volume: 45, Issue:11

    Topics: Adult; Body Weight; Breast Feeding; Child, Preschool; Chromatography, High Pressure Liquid; Diabetes

2002
Is programming of glucocorticoid receptor expression by prenatal dexamethasone in the rat secondary to metabolic derangement in adulthood?
    European journal of endocrinology, 2003, Volume: 148, Issue:1

    Topics: Animals; Appetite; Body Weight; Corticosterone; Dexamethasone; Female; Gene Expression; Glucocortico

2003
Hypoglycemia and reduced feed intake in broiler chickens treated with metformin.
    Poultry science, 2003, Volume: 82, Issue:1

    Topics: Animals; Blood Glucose; Body Weight; Chickens; Eating; Fatty Acids, Nonesterified; Glucagon; Insulin

2003
Type 2 diabetes presenting as diabetic ketoacidosis in adolescence.
    Diabetic medicine : a journal of the British Diabetic Association, 2003, Volume: 20, Issue:5

    Topics: Acanthosis Nigricans; Adolescent; Blood Glucose; Body Weight; C-Peptide; Diabetes Mellitus, Type 2;

2003
Long-term efficacy of steady-dose metformin in type 2 diabetes mellitus: a retrospective study.
    Medical science monitor : international medical journal of experimental and clinical research, 2003, Volume: 9, Issue:6

    Topics: Body Weight; Diabetes Mellitus, Type 2; Drug Therapy, Combination; Female; Follow-Up Studies; Humans

2003
Metformin, pre-eclampsia, and pregnancy outcomes in women with polycystic ovary syndrome.
    Diabetic medicine : a journal of the British Diabetic Association, 2004, Volume: 21, Issue:8

    Topics: Adult; Birth Weight; Body Weight; Diabetes, Gestational; Female; Gestational Age; HELLP Syndrome; Hu

2004
Effect of N-benzoyl-D-phenylalanine and metformin on carbohydrate metabolic enzymes in neonatal streptozotocin diabetic rats.
    Clinica chimica acta; international journal of clinical chemistry, 2005, Volume: 351, Issue:1-2

    Topics: Animals; Animals, Newborn; Blood Glucose; Body Weight; Carbohydrate Metabolism; Diabetes Mellitus, E

2005
Effect of metformin on the clinical and metabolic assessment of women with polycystic ovary syndrome.
    Gynecological endocrinology : the official journal of the International Society of Gynecological Endocrinology, 2004, Volume: 19, Issue:2

    Topics: Adolescent; Adult; Blood Glucose; Body Mass Index; Body Weight; Female; Glucose Tolerance Test; Huma

2004
[Short-term and long-term effect of metformin in type 1 diabetics].
    Vnitrni lekarstvi, 2001, Volume: 47, Issue:2

    Topics: Adult; Body Weight; Diabetes Mellitus, Type 1; Drug Therapy, Combination; Follow-Up Studies; Humans;

2001
Metformin treatment restores the altered microvascular reactivity in neonatal streptozotocin-induced diabetic rats increasing NOS activity, but not NOS expression.
    Life sciences, 2005, Oct-07, Volume: 77, Issue:21

    Topics: Animals; Animals, Newborn; Body Weight; Capillaries; Diabetes Mellitus, Experimental; Eating; Glucos

2005
Rosiglitazone plus metformin is effective and well tolerated in clinical practice: results from large observational studies in people with type 2 diabetes.
    International journal of clinical practice, 2005, Volume: 59, Issue:10

    Topics: Aged; Blood Pressure; Body Weight; Cohort Studies; Diabetes Mellitus, Type 2; Drug Therapy, Combinat

2005
Tissue-specific regulation of malonyl-CoA decarboxylase activity in OLETF rats.
    Diabetes, obesity & metabolism, 2006, Volume: 8, Issue:2

    Topics: Animals; Body Weight; Carboxy-Lyases; Cholesterol; Fasting; Fatty Acids, Nonesterified; Glucose; Hyp

2006
Stability of body weight in type 2 diabetes.
    Diabetes care, 2006, Volume: 29, Issue:3

    Topics: Adult; Aged; Body Mass Index; Body Weight; Diabetes Mellitus, Type 2; Humans; Insulin; Male; Metform

2006
Treatment escalation and rise in HbA1c following successful initial metformin therapy.
    Diabetes care, 2006, Volume: 29, Issue:3

    Topics: Body Weight; Diabetes Mellitus, Type 2; Female; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Ma

2006
Prenatal growth restraint followed by catch-up of weight: a hyperinsulinemic pathway to polycystic ovary syndrome.
    Fertility and sterility, 2006, Volume: 86 Suppl 1

    Topics: Aging; Androgen Antagonists; Body Weight; Child; Drug Therapy, Combination; Female; Fetal Developmen

2006
Changes in patient weight and the impact of antidiabetic therapy during the first 5 years after diagnosis of diabetes mellitus.
    Diabetologia, 2006, Volume: 49, Issue:9

    Topics: Age Factors; Aged; Body Mass Index; Body Weight; Diabetes Mellitus; Diabetes Mellitus, Type 2; Femal

2006
Effects of glibornuride versus metformin on eye lenses and skin in experimental diabetes.
    Arzneimittel-Forschung, 2006, Volume: 56, Issue:7

    Topics: Animals; Blood Glucose; Body Weight; Crystallins; Diabetes Mellitus, Experimental; Electrophoresis,

2006
Anti-diabetic effects of Sutherlandia frutescens in Wistar rats fed a diabetogenic diet.
    Journal of ethnopharmacology, 2007, Jan-03, Volume: 109, Issue:1

    Topics: Anesthesia; Animals; Blood Glucose; Body Weight; Diet; Dietary Fats; Glucose; Glycogen; Hyperinsulin

2007
The CC genotype of the GNAS T393C polymorphism is associated with obesity and insulin resistance in women with polycystic ovary syndrome.
    European journal of endocrinology, 2006, Volume: 155, Issue:5

    Topics: Androgens; Body Weight; Chromogranins; Female; Genotype; GTP-Binding Protein alpha Subunits, Gs; Hum

2006
Long-term efficacy of metformin therapy in nonobese individuals with type 2 diabetes.
    Diabetes care, 2006, Volume: 29, Issue:11

    Topics: Administration, Oral; Aged; Blood Glucose; Body Mass Index; Body Weight; Databases, Factual; Diabete

2006
Weight changes following the initiation of new anti-hyperglycaemic therapies.
    Diabetes, obesity & metabolism, 2007, Volume: 9, Issue:1

    Topics: Adult; Aged; Body Weight; Diabetes Mellitus, Type 2; Female; Follow-Up Studies; Humans; Hypoglycemic

2007
Sleep apnea is induced by a high-fat diet and reversed and prevented by metformin in non-obese rats.
    Obesity (Silver Spring, Md.), 2007, Volume: 15, Issue:6

    Topics: Animals; Body Weight; Diet, Atherogenic; Dietary Fats; Drug Evaluation, Preclinical; Hypoglycemic Ag

2007
Metformin improves polycystic ovary syndrome symptoms irrespective of pre-treatment insulin resistance.
    European journal of endocrinology, 2007, Volume: 157, Issue:5

    Topics: Body Weight; Female; Humans; Insulin Resistance; Metformin; Obesity; Overweight; Polycystic Ovary Sy

2007
Clinical predictors of disease progression and medication initiation in untreated patients with type 2 diabetes and A1C less than 7%.
    Diabetes care, 2008, Volume: 31, Issue:3

    Topics: Age Factors; Aged; Body Weight; Diabetes Mellitus, Type 2; Disease Progression; Female; Glycated Hem

2008
Clinical decisions. Management of type 2 diabetes--polling results.
    The New England journal of medicine, 2008, Feb-14, Volume: 358, Issue:7

    Topics: Body Weight; Cost-Benefit Analysis; Diabetes Mellitus, Type 2; Drug Therapy, Combination; Exenatide;

2008
Plasma high density lipoprotein cholesterol in streptozotocin diabetic and non-diabetic mice after prolonged administration of glibenclamide, chlorpropamide and metformin.
    Diabete & metabolisme, 1981, Volume: 7, Issue:4

    Topics: Animals; Blood Glucose; Body Weight; Chlorpropamide; Cholesterol; Cholesterol, HDL; Diabetes Mellitu

1981
[Effect of long-term metformin treatment on the development of diabetes in genetically diabetic mice (DBM) (author's transl)].
    Diabete & metabolisme, 1981, Volume: 7, Issue:4

    Topics: Animals; Blood Glucose; Body Weight; Diabetes Mellitus; Female; Glycated Hemoglobin; Insulin; Islets

1981
General practice care of non-insulin-dependent diabetes with fasting blood glucose measurements.
    The American journal of medicine, 1982, Volume: 73, Issue:5

    Topics: Adult; Aged; Blood Glucose; Body Weight; Diabetes Mellitus; Family Practice; Fasting; Female; Glycat

1982
Metformin induces an agonist-specific increase in albumin production by primary cultured rat hepatocytes.
    Biochemical pharmacology, 1995, Sep-07, Volume: 50, Issue:6

    Topics: Albumins; Animals; Body Weight; Cell Survival; Cells, Cultured; Epidermal Growth Factor; Insulin; In

1995
Effects of metformin treatment on glucose transporter proteins in subcellular fractions of skeletal muscle in (fa/fa) Zucker rats.
    British journal of pharmacology, 1995, Volume: 115, Issue:7

    Topics: Animals; Blood Glucose; Body Weight; Feeding Behavior; Glucose Transporter Type 1; Glucose Transport

1995
Anorectic effect of metformin in obese Zucker rats: lack of evidence for the involvement of neuropeptide Y.
    European journal of pharmacology, 1995, Jan-24, Volume: 273, Issue:1-2

    Topics: Administration, Oral; Animals; Appetite Depressants; Blood Glucose; Body Weight; Drinking; Eating; H

1995
Metformin decreases plasma insulin levels and systolic blood pressure in spontaneously hypertensive rats.
    The American journal of physiology, 1994, Volume: 267, Issue:4 Pt 2

    Topics: Aging; Animals; Blood Glucose; Body Weight; Hypertension; Insulin; Insulin Secretion; Male; Metformi

1994
[Metformin undervalued].
    Deutsche medizinische Wochenschrift (1946), 1996, Mar-08, Volume: 121, Issue:10

    Topics: Aged; Body Weight; Diabetes Mellitus, Type 2; Humans; Hypoglycemic Agents; Metformin; Middle Aged

1996
Metformin decreases blood pressure and obesity in OLETF rats via improvement of insulin resistance.
    Hypertension research : official journal of the Japanese Society of Hypertension, 1996, Volume: 19, Issue:1

    Topics: Aging; Animals; Blood Glucose; Blood Pressure; Blotting, Northern; Body Weight; Diabetes Mellitus, T

1996
Prevention of hyperglycemia in the Zucker diabetic fatty rat by treatment with metformin or troglitazone.
    The American journal of physiology, 1996, Volume: 271, Issue:4 Pt 1

    Topics: Age Factors; Animals; Body Weight; Chromans; Diabetes Mellitus, Type 2; Fatty Acids, Nonesterified;

1996
[The effect of metformin on lactate levels in type II diabetes].
    Vnitrni lekarstvi, 1996, Volume: 42, Issue:11

    Topics: Body Weight; Cholesterol; Diabetes Mellitus, Type 2; Glycated Hemoglobin; Humans; Hypoglycemic Agent

1996
[Comparison of two treatment models in type-II diabetic patients with poor metabolic control: Preformed combination of glibenclamide 2,5 mg + metformin 400 mg or mono-therapy with sulfonylurea at maximal doses? An evaluation at six months].
    Minerva endocrinologica, 1996, Volume: 21, Issue:3

    Topics: Blood Glucose; Body Weight; Diabetes Mellitus, Type 2; Drug Administration Schedule; Drug Combinatio

1996
Increased alanine uptake and lipid synthesis from alanine in isolated hepatocytes of Wistar-Kyoto fatty rats: an inhibitory effect of biguanides.
    Canadian journal of physiology and pharmacology, 1997, Volume: 75, Issue:3

    Topics: Aging; Alanine; Animals; Body Weight; Buformin; Cells, Cultured; Diabetes Mellitus, Experimental; Di

1997
A retrospective analysis of the efficacy and safety of metformin in the African-American patient.
    Journal of the National Medical Association, 1997, Volume: 89, Issue:11

    Topics: Adult; Aged; Aged, 80 and over; Black People; Body Weight; Diabetes Mellitus, Type 2; Drug Therapy,

1997
Effect of masoprocol on carbohydrate and lipid metabolism in a rat model of Type II diabetes.
    Diabetologia, 1999, Volume: 42, Issue:1

    Topics: Adipocytes; Animals; Antioxidants; Blood Glucose; Body Weight; Diabetes Mellitus, Experimental; Diab

1999
Review of management of type 2 diabetes mellitus.
    Journal of clinical pharmacy and therapeutics, 1998, Volume: 23, Issue:6

    Topics: Aged; Body Weight; Contraindications; Diabetes Mellitus, Type 2; Drug Therapy, Combination; Female;

1998
Safety and efficacy of metformin in a restricted formulary.
    The American journal of managed care, 1999, Volume: 5, Issue:1

    Topics: Blood Pressure; Body Weight; California; Diabetes Mellitus, Type 2; Female; Formularies, Hospital as

1999
Metformin reverses fatty liver disease in obese, leptin-deficient mice.
    Nature medicine, 2000, Volume: 6, Issue:9

    Topics: Adenosine Triphosphate; Adipose Tissue; Animals; Body Weight; Energy Intake; Energy Metabolism; Fatt

2000
Beneficial insulin-sensitizing and vascular effects of S15261 in the insulin-resistant JCR:LA-cp rat.
    The Journal of pharmacology and experimental therapeutics, 2000, Volume: 295, Issue:2

    Topics: Animals; Blood Glucose; Body Weight; Chromans; Eating; Fluorenes; Gene Expression; Glucose Tolerance

2000
Metformin reduces weight, centripetal obesity, insulin, leptin, and low-density lipoprotein cholesterol in nondiabetic, morbidly obese subjects with body mass index greater than 30.
    Metabolism: clinical and experimental, 2001, Volume: 50, Issue:7

    Topics: Adult; Aged; Body Mass Index; Body Weight; Cholesterol, LDL; Coronary Disease; Fasting; Female; Huma

2001
Mechanism of fat-induced hepatic gluconeogenesis: effect of metformin.
    American journal of physiology. Endocrinology and metabolism, 2001, Volume: 281, Issue:2

    Topics: Administration, Oral; Alanine; Animals; Blood Glucose; Body Weight; Dietary Fats; Fatty Acids, Nones

2001
Exercise adds to metformin and acarbose efficacy in db/db mice.
    Metabolism: clinical and experimental, 2001, Volume: 50, Issue:9

    Topics: Acarbose; Animals; Blood Glucose; Body Weight; Diabetes Mellitus, Type 2; Disease Models, Animal; Ea

2001
Metformin in non-alcoholic steatohepatitis.
    Lancet (London, England), 2001, Sep-15, Volume: 358, Issue:9285

    Topics: Adult; Alanine Transaminase; Body Mass Index; Body Weight; Fatty Liver; Female; Humans; Hypoglycemic

2001
Biochemical and body weight changes with metformin in polycystic ovary syndrome.
    Clinical and experimental obstetrics & gynecology, 2001, Volume: 28, Issue:4

    Topics: Adult; Body Weight; Female; Humans; Hypoglycemic Agents; Insulin; Menstruation; Metformin; Obesity;

2001
Metformin therapy throughout pregnancy reduces the development of gestational diabetes in women with polycystic ovary syndrome.
    Fertility and sterility, 2002, Volume: 77, Issue:3

    Topics: Adult; Blood Glucose; Body Weight; Cohort Studies; Diabetes Complications; Diabetes Mellitus; Diabet

2002
Inhibition of gluconeogenesis by vanadium and metformin in kidney-cortex tubules isolated from control and diabetic rabbits.
    Biochemical pharmacology, 2002, Apr-01, Volume: 63, Issue:7

    Topics: Animals; Blood Glucose; Body Weight; Diabetes Mellitus; Gluconeogenesis; Hypoglycemic Agents; Kidney

2002
Effects of combined pioglitazone and metformin on diabetes and obesity in Wistar fatty rats.
    Clinical and experimental pharmacology & physiology, 2002, Volume: 29, Issue:4

    Topics: Adipose Tissue; Animals; Body Weight; Diabetes Mellitus; Drug Therapy, Combination; Eating; Glycogen

2002
Treatment of type 2 diabetes mellitus in children and adolescents.
    Journal of pediatric endocrinology & metabolism : JPEM, 2002, Volume: 15 Suppl 1

    Topics: Adolescent; Black People; Blood Glucose; Body Weight; Child; Diabetes Mellitus, Type 2; Drug Therapy

2002
Hypolipidemic effects of metformin in hyperprebetalipoproteinemia.
    Diabete & metabolisme, 1976, Volume: 2, Issue:3

    Topics: Adult; Blood Glucose; Body Weight; Cholesterol; Diabetes Complications; Female; Glucose Tolerance Te

1976
Treatment of hypertriglyceridemia with metformin. Effectiveness and analỳsis of results.
    Atherosclerosis, 1977, Volume: 26, Issue:4

    Topics: Adult; Age Factors; Blood Glucose; Body Weight; Cholesterol; Drug Evaluation; Drug Resistance; Femal

1977
Treatment of normal-weight diabetics.
    British medical journal, 1978, Feb-25, Volume: 1, Issue:6111

    Topics: Body Weight; Diabetes Mellitus; Diabetic Ketoacidosis; Humans; Metformin

1978
Effects of metformin on glucose metabolism of isolated perfused rat skeletal muscle.
    Arzneimittel-Forschung, 1977, Volume: 27, Issue:8

    Topics: Adenosine Triphosphate; Animals; Body Weight; Creatine Kinase; Female; Glucose; Lactates; Metformin;

1977
Treatment of normal-weight diabetics.
    British medical journal, 1978, Jan-21, Volume: 1, Issue:6106

    Topics: Aged; Body Weight; Diabetes Mellitus; Humans; Metformin; Middle Aged; Obesity

1978
[Therapy of diabetes mellitus with oral drugs].
    Medizinische Klinik, 1978, Dec-08, Volume: 73, Issue:49

    Topics: Acidosis; Body Weight; Diabetes Mellitus; Drug Tolerance; Humans; Metformin; Obesity; Sulfonylurea C

1978
A comparison of phenformin and metformin in the treatment of maturity onset diabetes.
    Diabete & metabolisme, 1977, Volume: 3, Issue:3

    Topics: Adult; Aged; Blood Glucose; Body Weight; Diabetes Mellitus; Dose-Response Relationship, Drug; Female

1977
[Proinsulin and insulin secretion in obese females before and after administration of metformin].
    Arzneimittel-Forschung, 1975, Volume: 25, Issue:4

    Topics: Adult; Blood Glucose; Body Weight; Cholesterol; Diet, Reducing; Female; Glucose Tolerance Test; Huma

1975
Influence of metformin on arginine-induced glucagon secretion in human diabetes.
    Diabete & metabolisme, 1975, Volume: 1

    Topics: Adult; Aged; Arginine; Blood Glucose; Body Weight; Diabetes Mellitus; Fatty Acids, Nonesterified; Fe

1975
Subchronic treatment with metformin produces anorectic effect and reduces hyperinsulinemia in genetically obese Zucker rats.
    Life sciences, 1992, Volume: 50, Issue:23

    Topics: Animals; Appetite Depressants; Blood Glucose; Body Weight; Corticosterone; Digestive System; Eating;

1992
Mechanism of metformin action in obese and lean noninsulin-dependent diabetic subjects.
    The Journal of clinical endocrinology and metabolism, 1991, Volume: 73, Issue:6

    Topics: Blood Glucose; Body Weight; Diabetes Mellitus; Diabetes Mellitus, Type 2; Fasting; Female; Glucose;

1991
A comparison of treatment with metformin and gliclazide in patients with non-insulin-dependent diabetes.
    European journal of clinical pharmacology, 1988, Volume: 34, Issue:2

    Topics: Adult; Aged; Blood Glucose; Body Weight; Diabetes Mellitus, Type 2; Female; Gliclazide; Humans; Insu

1988
Energy expenditure in non-insulin dependent diabetic subjects on metformin or sulphonylurea therapy.
    Clinical science (London, England : 1979), 1987, Volume: 73, Issue:1

    Topics: Adult; Blood Glucose; Body Weight; Diabetes Mellitus, Type 2; Energy Metabolism; Fatty Acids, Nonest

1987
Anorectic effect of metformin in lean and genetically obese hyperglycaemic (ob/ob) mice.
    Archives internationales de pharmacodynamie et de therapie, 1986, Volume: 282, Issue:2

    Topics: Animals; Appetite Depressants; Blood Glucose; Body Weight; Eating; Injections, Intraperitoneal; Metf

1986
Effect of metformin on peripheral insulin sensitivity in non insulin dependent diabetes mellitus.
    Diabete & metabolisme, 1986, Volume: 12, Issue:6

    Topics: Adult; Aged; Blood Glucose; Body Weight; Diabetes Mellitus, Type 2; Female; Glycated Hemoglobin; Hum

1986
Dimethylbiguanide-evoked increase of anticoagulant elimination not associated with induction of drug metabolizing enzymes.
    Biochemical medicine, 1974, Volume: 11, Issue:4

    Topics: Aminopyrine N-Demethylase; Animals; Benzopyrenes; Body Weight; Carbon Radioisotopes; Chromatography,

1974
Metformin administration in hyperlipidemic states.
    Acta medica Scandinavica, 1971, Volume: 190, Issue:6

    Topics: Adult; Aged; Blood Glucose; Blood Protein Electrophoresis; Body Weight; Cholesterol; Electrophoresis

1971
[Disturbance of intestinal absorption following metformin therapy (observations on the mode of action of biguanides].
    Diabetologia, 1969, Volume: 5, Issue:6

    Topics: Body Weight; Diabetes Mellitus; Humans; Intestinal Absorption; Lipids; Metformin; Obesity; Vitamin B

1969
Observations on the mechanism of increased weight loss during metformin administration in obesity.
    Acta endocrinologica, 1968, Volume: 57, Issue:4

    Topics: Body Weight; Carbohydrate Metabolism; Diet Therapy; Female; Humans; Lipid Metabolism; Metformin; Met

1968
[Treatment of diabetes mellitus with metformin].
    Lakartidningen, 1968, Nov-20, Volume: 65, Issue:47

    Topics: Adult; Aged; Body Weight; Chlorpropamide; Diabetes Mellitus; Drug Synergism; Female; Humans; Male; M

1968
[On the clinical use of biguanides].
    Arzneimittel-Forschung, 1969, Volume: 19, Issue:4

    Topics: Aged; Biguanides; Blood Glucose; Body Weight; Cholesterol; Depression, Chemical; Diabetes Mellitus;

1969
[Therapeutic possibilities in diabetes mellitus with biguanides. Clinical experiences in 122 diabetics with dimethylbiguanide(Glucophage)].
    Schweizerische medizinische Wochenschrift, 1966, Oct-08, Volume: 96, Issue:40

    Topics: Adolescent; Adult; Biguanides; Body Weight; Chemical Phenomena; Chemistry; Diabetes Mellitus; Diet,

1966